Academic literature on the topic 'AKT PHOSPHORYLATION'
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Journal articles on the topic "AKT PHOSPHORYLATION"
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Ono, Hiraku, Hideyuki Sakoda, Midori Fujishiro, Motonobu Anai, Akifumi Kushiyama, Yasushi Fukushima, Hideki Katagiri, et al. "Carboxy-terminal modulator protein induces Akt phosphorylation and activation, thereby enhancing antiapoptotic, glycogen synthetic, and glucose uptake pathways." American Journal of Physiology-Cell Physiology 293, no. 5 (November 2007): C1576—C1585. http://dx.doi.org/10.1152/ajpcell.00570.2006.
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Carboxy-terminal modulator protein (CTMP) was identified as binding to the carboxy terminus of Akt and inhibiting the phosphorylation and activation of Akt. In contrast to a previous study, we found CTMP overexpression to significantly enhance Akt phosphorylation at both Thr308and Ser473as well as the kinase activity of Akt, while phosphatidylinositol 3-kinase (PI3-kinase) activity was unaffected. Translocation of Akt to the membrane fraction was also markedly increased in response to overexpression of CTMP, with no change in the whole cellular content of Akt. Furthermore, the phosphorylations of GSK-3β and Foxo1, well-known substrates of Akt, were increased by CTMP overexpression. On the other hand, suppression of CTMP with small interfering RNA partially but significantly attenuated this Akt phosphorylation. The cellular activities reportedly mediated by Akt activation were also enhanced by CTMP overexpression. UV-B-induced apoptosis of HeLa cells was significantly reversed not only by overexpression of the active mutant of Akt (myr-Akt) but also by that of CTMP. Increases in glucose transport activity and glycogen synthesis were also induced by overexpression of either myr-Akt or CTMP in 3T3-L1 adipocytes. Taking these results into consideration, it can be concluded that CTMP induces translocation of Akt to the membrane and thereby increases the level of Akt phosphorylation. As a result, CTMP enhances various cellular activities that are principally mediated by the PI3-kinase/Akt pathway.
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Hausenloy, Derek J., A. Tsang, Mihaela M. Mocanu, and Derek M. Yellon. "Ischemic preconditioning protects by activating prosurvival kinases at reperfusion." American Journal of Physiology-Heart and Circulatory Physiology 288, no. 2 (February 2005): H971—H976. http://dx.doi.org/10.1152/ajpheart.00374.2004.
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Pharmacological activation of the prosurvival kinases Akt and ERK-1/2 at reperfusion, after a period of lethal ischemia, protects the heart against ischemia-reperfusion injury. We hypothesized that ischemic preconditioning (IPC) protects the heart by phosphorylating the prosurvival kinases Akt and ERK-1/2 at reperfusion. In isolated perfused Sprague-Dawley rat hearts subjected to 35 min of lethal ischemia, the phosphorylation states of Akt, ERK-1/2, and p70 S6 kinase (p70S6K) were determined after 15 min of reperfusion, and infarct size was measured after 120 min of reperfusion. IPC induced a biphasic response in Akt and ERK-1/2 phosphorylation during the preconditioning and reperfusion phases after the period of lethal ischemia. IPC induced a fourfold increase in Akt, ERK-1/2, and p70S6K phosphorylation at reperfusion and reduced the infarct risk-to-volume ratio (56.9 ± 5.7 and 20.9 ± 3.6% for control and IPC, respectively, P < 0.01). Inhibiting the IPC-induced phosphorylation of Akt, ERK-1/2, and p70S6K at reperfusion with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 or the MEK-1/2 inhibitor PD-98059 abrogated IPC-induced protection (46.3 ± 5.8, 49.2 ± 4.0, and 20.9 ± 3.6% for IPC + LY-294002, IPC + PD-98059, and IPC, respectively, P < 0.01), demonstrating that the phosphorylation of these kinases at reperfusion is required for IPC-induced protection. In conclusion, we demonstrate that the reperfusion phase following sustained ischemia plays an essential role in mediating IPC-induced protection. Specifically, we demonstrate that IPC protects the heart by phosphorylating the prosurvival kinases Akt and ERK-1/2 at reperfusion.
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Ashcroft, Margaret, Robert L. Ludwig, Douglas B. Woods, Terry D. Copeland, H. Oliver Weber, Elizabeth J. MacRae, and Karen H. Vousden. "Phosphorylation of HDM2 by Akt." Oncogene 21, no. 13 (March 2002): 1955–62. http://dx.doi.org/10.1038/sj.onc.1205276.
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Kim, Albert H., Gus Khursigara, Xuan Sun, Thomas F. Franke, and Moses V. Chao. "Akt Phosphorylates and Negatively Regulates Apoptosis Signal-Regulating Kinase 1." Molecular and Cellular Biology 21, no. 3 (February 1, 2001): 893–901. http://dx.doi.org/10.1128/mcb.21.3.893-901.2001.
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ABSTRACT The Akt family of serine/threonine-directed kinases promotes cellular survival in part by phosphorylating and inhibiting death-inducing proteins. Here we describe a novel functional interaction between Akt and apoptosis signal-regulating kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase. Akt decreased ASK1 kinase activity stimulated by both oxidative stress and overexpression in 293 cells by phosphorylating a consensus Akt site at serine 83 of ASK1. Activation of the phosphoinositide 3-kinase (PI3-K)/Akt pathway also inhibited the serum deprivation-induced activity of endogenous ASK1 in L929 cells. An association between Akt and ASK1 was detected in cells by coimmunoprecipitation. Phosphorylation by Akt inhibited ASK1-mediated c-Jun N-terminal kinase and activating transcription factor 2 activities in intact cells. Finally, activation of the PI3-K/Akt pathway reduced apoptosis induced by ASK1 in a manner dependent on phosphorylation of serine 83 of ASK1. These results provide the first direct link between Akt and the family of stress-activated kinases.
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Romic, Snjezana, Snezana Tepavcevic, Zorica Zakula, Tijana Milosavljevic, Mojca Stojiljkovic, Maja Zivkovic, Milan Popovic, Aleksandra Stankovic, and Goran Koricanac. "Does oestradiol attenuate the damaging effects of a fructose-rich diet on cardiac Akt/endothelial nitric oxide synthase signalling?" British Journal of Nutrition 109, no. 11 (October 16, 2012): 1940–48. http://dx.doi.org/10.1017/s0007114512004114.
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Fructose-rich diets (FRD) cause cardiac insulin resistance manifested by impairment of Akt/endothelial NO synthase (eNOS) signalling. In contrast, oestradiol (E2) activates this signalling pathway in the heart. To study the ability of E2 to revert the detrimental effect of fructose on cardiac Akt/eNOS, female rats were subjected to a FRD and ovariectomy followed with or without E2 replacement. We also analysed the effects of the FRD and E2 on cardiac extracellular signal-regulated kinase (Erk 1/2) signalling related to their role in cardiac hypertrophy development. Expression of Akt, eNOS and Erk 1/2, as well as regulatory phosphorylations of these molecules were determined. The protein expression of cardiac Akt and eNOS was not affected by the diet or E2 treatment. However, the FRD was accompanied by a decrease in Akt phosphorylation at Ser473 and Thr308, and eNOS at Ser1177, while the phosphorylation of eNOS at Thr495 was increased. E2 replacement in ovariectomised fructose-fed rats caused a reversion of the diet effect on Akt and eNOS serine phosphorylation, but mostly had no effect on threonine phosphorylation of the molecules. The FRD and E2 treatment did not influence Erk 1/2 expression and phosphorylation and heart mass as well. The data show that E2 selectively suppress the negative effects of a FRD on Akt/eNOS signalling and probably point to the different effects of E2 on kinase/phosphatase pathways responsible for phosphorylation/dephosphorylation of Akt and eNOS. Furthermore, the results suggest that the heart of females in the reproductive period is partially protected against the damaging effects of increased fructose intake.
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Dunn, Ewan F., Rachel Fearns, and John H. Connor. "Akt Inhibitor Akt-IV Blocks Virus Replication through an Akt-Independent Mechanism." Journal of Virology 83, no. 22 (September 9, 2009): 11665–72. http://dx.doi.org/10.1128/jvi.01092-09.
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ABSTRACT Many viruses activate the phosphatidylinositol 3′-kinase (PI3k)/Akt intracellular signaling pathway to promote viral replication. We have analyzed whether a rapidly replicating rhabdovirus, vesicular stomatitis virus (VSV), requires the PI3k/Akt signaling pathway for its replication. Through the use of chemical inhibitors of PI3k and Akt, we show that VSV replication and cytopathic effects do not require activation of these kinases. Inhibitors that block the activating phosphorylations of Akt at threonine 308 (Thr308) and serine 473 (Ser473) did not inhibit VSV protein expression or the induction of the cytopathic effects of VSV. One compound, Akt inhibitor Akt-IV, inhibited the replication of VSV, respiratory syncytial virus, and vaccinia virus but increased the phosphorylation of Akt at positions Thr308 and Ser473 and did not inhibit Akt kinase activity in vitro. Together, our data suggest that the PI3k/Akt pathway is of limited relevance to the replication of VSV but that Akt inhibitor Akt-IV is a novel broad-spectrum antiviral compound with a mechanism differing from that of its previously reported effect on the PI3k/Akt pathway. Identification of other targets for this compound may define a new approach for blocking virus replication.
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Kim, Ji-Eun, Duk-Shin Lee, Tae-Hyun Kim, Hana Park, and Tae-Cheon Kang. "Distinct Roles of CK2- and AKT-Mediated NF-κB Phosphorylations in Clasmatodendrosis (Autophagic Astroglial Death) within the Hippocampus of Chronic Epilepsy Rats." Antioxidants 12, no. 5 (April 28, 2023): 1020. http://dx.doi.org/10.3390/antiox12051020.
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The downregulation of glutathione peroxidase-1 (GPx1) plays a role in clasmatodendrosis (an autophagic astroglial death) in the hippocampus of chronic epilepsy rats. Furthermore, N-acetylcysteine (NAC, a GSH precursor) restores GPx1 expression in clasmatodendritic astrocytes and alleviates this autophagic astroglial death, independent of nuclear factor erythroid-2-related factor 2 (Nrf2) activity. However, the regulatory signal pathways of these phenomena have not been fully explored. In the present study, NAC attenuated clasmatodendrosis by alleviating GPx1 downregulation, casein kinase 2 (CK2)-mediated nuclear factor-κB (NF-κB) serine (S) 529 and AKT-mediated NF-κB S536 phosphorylations. 2-[4,5,6,7-Tetrabromo-2-(dimethylamino)-1H-benzo[d]imidazole-1-yl]acetic acid (TMCB; a selective CK2 inhibitor) relieved clasmatodendritic degeneration and GPx1 downregulation concomitant with the decreased NF-κB S529 and AKT S473 phosphorylations. In contrast, AKT inhibition by 3-chloroacetyl-indole (3CAI) ameliorated clasmatodendrosis and NF-κB S536 phosphorylation, while it did not affect GPx1 downregulation and CK2 tyrosine (Y) 255 and NF-κB S529 phosphorylations. Therefore, these findings suggest that seizure-induced oxidative stress may diminish GPx1 expression by increasing CK2-mediated NF-κB S529 phosphorylation, which would subsequently enhance AKT-mediated NF-κB S536 phosphorylation leading to autophagic astroglial degeneration.
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Xiang, Binggang, Guoying Zhang, Junling Liu, Andrew J. Morris, Susan S. Smyth, T. Kent Gartner, and Zhenyu Li. "A novel P2Y12-Independent Signaling Pathway Mediating Akt Phosphorylation In Response to Thrombin Receptors." Blood 116, no. 21 (November 19, 2010): 3191. http://dx.doi.org/10.1182/blood.v116.21.3191.3191.
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Abstract Abstract 3191 The serine-threonine kinase Akt plays an important role in regulating platelet activation. Stimulation of platelets with various agonists results in Akt activation as indicated by Akt phosphorylation. However, the mechanisms of Akt phosphorylation in platelets are not completely understood. It has been previously shown that Akt phosphorylation in response to thrombin receptors is dependent on Gi signaling activated primarily by secreted ADP through its receptor P2Y12. By using P2Y12 knockout mice combined with recombinant CHO models, we demonstrate a Gi-independent pathway for Akt phosphorylation in response to thrombin. Although Akt phosphorylation in response to low dose thrombin or the PAR4 thrombin receptor peptide AYPGKF was abolished in P2Y12 deficient platelets, at high concentrations, they stimulated substantial phosphorylation of both Akt residues Thr308 and Ser473 in P2Y12 deficient platelets, demonstrating that there are P2Y12-dependent and -independent pathways contributing to Akt phosphorylation in response to thrombin receptors. Thrombin or AYPGKF repressed forskolin-induced cAMP production in the wild type mouse platelets but not in the P2Y12 deficient platelets, suggesting that Gi activation by thrombin or AYPGKF is dependent on ADP receptor P2Y12. Therefore, thrombin- or AYPGKF-induced Akt phosphorylation in P2Y12 deficient platelets is Gi independent. AYPGKF-induced Akt phosphorylation was enhanced by expression of recombinant PAR4 cDNA in CHO cells, demonstrating that stimulation of thrombin receptor PAR4 is able to elicit Akt phosphorylation in the absence of platelet secretion. It is unlikely that PAR4-induced Akt phosphorylation in CHO cells involves the P2Y12 pathway, because CHO cells apparently do not express functional P2Y12. This conclusion is supported by the observation that ADP failed to stimulate Akt phosphorylation and inhibit forskolin-induced cAMP production in CHO cells. Unlike thrombin, U46619-induced Akt phosphorylation was dramatically decreased by P2Y12 deficiency, suggesting that TXA2-induced Akt phosphorylation is largely P2Y12 dependent. In addition, P2Y12-independent Akt phosphorylation was not inhibited by the integrin inhibitor peptide RGDS or integrin β3 deficiency, demonstrating that integrin αIIbβ3 outside-in signaling is not required for thrombin-induced, P2Y12-independent, Akt phosphorylation. Furthermore, Akt phosphorylation in response to thrombin or AYPGKF in P2Y12 deficient platelets was inhibited by the calcium chelator dimethyl-BAPTA, the Src family kinase inhibitor PP2, or PI3K inhibitors, but was not affected by PKC inhibitors. Thus, our results reveal a novel P2Y12-independent signaling pathway mediating Akt phosphorylation in response to thrombin receptors. Disclosures: No relevant conflicts of interest to declare.
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Kim, Soochong, Jianguo Jin, and Satya P. Kunapuli. "Relative contribution of G-protein-coupled pathways to protease-activated receptor-mediated Akt phosphorylation in platelets." Blood 107, no. 3 (February 1, 2006): 947–54. http://dx.doi.org/10.1182/blood-2005-07-3040.
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AbstractProtease-activated receptors (PARs) activate Gq and G12/13 pathways, as well as Akt (protein kinase B [PKB/Akt]) in platelets. However, the relative contribution of different G-protein pathways to Akt phosphorylation has not been elucidated. We investigated the contribution of Gq and G12/13 to Gi/Gz-mediated Akt phosphorylation downstream of PAR activation. Selective G12/13 activation failed to cause Akt phosphorylation in human and Gαq-deficient mouse platelets. However, supplementing Gi/Gz signaling to G12/13 caused significant increase in Akt phosphorylation, confirming that G12/13 potentiates Akt phosphorylation. Inhibition of PAR-mediated Akt phosphorylation in the presence of the Gq-selective inhibitor YM-254890 was restored to the normal extent achieved by PAR agonists if supplemented with Gi signaling, indicating that Gq does not have any direct effect on Akt phosphorylation. Selective G12/13 activation resulted in Src kinase activation, and Akt phosphorylation induced by costimulation of G12/13 and Gi/Gz was inhibited by a Src kinase inhibitor but not by a Rho kinase inhibitor. These data demonstrate that G12/13, but not Gq, is essential for thrombin-induced Akt phosphorylation in platelets, whereas Gq indirectly contributes to Akt phosphorylation through Gi stimulation by secreted ADP. G12/13 activation might mediate its potentiating effect through Src activation, and Src kinases play an important role in thrombin-mediated Akt phosphorylation.
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Gayer, Christopher P., Lakshmi S. Chaturvedi, Shouye Wang, Brittany Alston, Thomas L. Flanigan, and Marc D. Basson. "Delineating the signals by which repetitive deformation stimulates intestinal epithelial migration across fibronectin." American Journal of Physiology-Gastrointestinal and Liver Physiology 296, no. 4 (April 2009): G876—G885. http://dx.doi.org/10.1152/ajpgi.90648.2008.
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Repetitive strain stimulates intestinal epithelial migration across fibronectin via focal adhesion kinase (FAK), Src, and extracellular signal-related kinase (ERK) although how these signals act and interact remains unclear. We hypothesized that PI3K is central to this pathway. We subjected Caco-2 and intestinal epithelial cell-6 cells to 10 cycles/min deformation on flexible fibronectin-coated membranes, assayed migration by wound closure, and signaling by immunoblots. Strain stimulated PI3K, AKT, glycogen synthase kinase (GSK), and p38 phosphorylation. Blocking each kinase prevented strain stimulation of migration. Blocking PI3K prevented strain-stimulated ERK and p38 phosphorylation. Blocking AKT did not. Downstream, blocking PI3K, AKT, or ERK inhibited strain-induced GSK-Ser9 phosphorylation. Upstream of AKT, reducing FAK or Rac1 by siRNA blocked strain-stimulated AKT phosphorylation, but inhibiting Src by PP2 or siRNA did not. Transfection with FAK point mutants at Tyr397, Tyr576/577, or Tyr925 demonstrated that only FAK925 phosphorylation is required for strain-stimulated AKT phosphorylation. Myosin light chain activation by strain required FAK, Rac1, PI3K, AKT, GSK, and ERK but not Src or p38. Finally, blebbistatin, a nonmuscle myosin II inhibitor, blocked the motogenic effect of strain downstream of myosin light chain. Thus strain stimulates intestinal epithelial migration across fibronectin by a complex pathway including Src, FAK, Rac1, PI3K, AKT, GSK, ERK, p38, myosin light chain, and myosin II.
Dissertations / Theses on the topic "AKT PHOSPHORYLATION"
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Schrötter, Sandra. "Specificity of developmental- and growth factor-dependent phosphorylation of Akt isoforms in neurons." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17593.
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Ein Signalweg während der neuronalen Entwicklung im adulten Gehirn ist der PI3K-PTEN-Akt Signalweg. Akt ist eine Kinase die drei verschiedene Isoformen besitzt, welche durch die Phosphorylierung von S473 und T308 aktiviert werden. KO Modelle der Isoformen haben gezeigt, dass nicht alle Funktionen von anderen Isoformen kompensiert werden können. Die genaue Rolle der einzelnen Isoformen in einem neuronalen Zusammenhang ist nur wenig untersucht. Ziel dieser Arbeit war, eine detaillierte Analyse der einzelnen Akt Isoformen nach der Aktivierung des PI3K-PTEN Signalweges. Dazu wurde im Labor eine neue Methode zur isoelektrischen Fokussierung etabliert., welche Proteine nach ihrer Ladung trennt und somit eine Analyse der Dynamik von Akt Phosphorylierungen in neuronalen Zellen erlaubt. Im Zuge dieser Arbeit konnten wir bisher unerkannte Merkmale der Akt Aktivierung und Phosphorylierung identifizieren. Wir konnten zeigen, dass die S473 und T308 Phosphorylierung in Neuroblastomazellen unabhängig voneinander auftreten kann und, dass verschiedene Akt1 Moleküle unterschiedlich auf die Inhibition von PI3K reagieren. Außerdem konnten wir Verschiebungen in der Aktivierung und in der Expression der unterschiedlichen Isoformen während der postnatalen Gehirnentwicklung der Ratte feststellen. Des Weiteren konnten wir zeigen, dass die Aktivierung von Akt von dem Signal und dem Alter der Neurone abhängig ist. Noch nicht vollständig differenzierte Neurone reagieren vor allem auf BDNF Stimulation, wohingegen adulte, differenzierte Neurone hauptsächlich auf EGF reagieren und dort explizit Akt2 über EGFR und PI3K-p110α Signale aktiviert wird. Im Gegensatz dazu führt der Verlust von PTEN zu einer Aktivierung von hauptsächlich Akt1. Zusammenfassend zeigt diese Arbeit einen komplexen Zusammenhang der Phosphorylierung von Akt auf, welcher Signal- und Entwicklungsabhängig ist bei dem unterschiedliche Akt Populationen auf Wachstumsfaktoren und auf PTEN Verlust reagieren.A major pathway involved in neuronal development is the PI3K-PTEN-Akt pathway. Akt comprises three isoforms, which are activated by phosphorylation of the residues S473 and T308. KO animals for the isoforms have shown differential as well as redundant functions of the three isoforms. However, their individual role in neuronal signaling pathways has not yet been studied in great detail. The aim of this study was to obtain further insight into differential Akt isoform signaling in response to changes in the activity of PI3K and PTEN pathway. A new isoelectric focusing method was established, which allowed us to separate Akt proteins according to their charge, therefore, providing a refined read-out to study dynamics of Akt phosphorylation in a neuronal background. In the course of this project we were able to identify previously undescribed features of Akt phosphorylation and activation. First, we could provide evidence for an uncoupling of the two activating phosphorylation events at S473 and T308 in neuroblastoma cells and differential sensitivities of Akt1 forms towards PI3K inhibition. Secondly, we found a transient shift in Akt isoform activation and abundance during postnatal rat brain development. Thirdly, we were able to show that the activation of different Akt isoforms is dependent of the upstream signal as well as the age of the neuron. Immature neurons were found to be highly responsive to BDNF treatment, whereas mature neurons were most responsive to EGF stimulation leading exclusively to activation of Akt2 in an EGFR- and PI3K/p110α-dependent manner. Stimulation of Akt phosphorylation by the loss of PTEN led to an activation of mainly Akt1 forms, which suggests inherent differences in the Akt pools that are accessible to growth factors dependent PI3Ks as compared to the pools that are controlled by PTEN. In summary, this thesis demonstrates the presence of complex phosphorylation events of Akt in a developmental- and signal-dependent manner in neurons.
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Lefevre, Carine. "Mécanismes de régulation de la balance prolifération/différenciation érythroïde par les facteurs de transcription GATA-1, FOG-1, E2F et la voie de signalisation Akt." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T010/document.
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Avec plus de 100 milliards de globules rouges produits chaque jour, le lignage érythroïde présente la plus grande capacité de production cellulaire chez le mammifère adulte. Cette production requiert une balance fine entre la prolifération cellulaire, régulée principalement par la voie de signalisation érythropoïétine (Epo)/PI3K/Akt, et la différenciation érythroïde induite par le couple de facteurs de transcription GATA-1/FOG-1. Des interconnexions entre ces deux grands systèmes ont été décrites dans le laboratoire : 1) le facteur de transcription GATA-1 est phosphorylé par Akt en réponse à l’Epo et cette phosphorylation semble avoir un rôle dans la différenciation érythroïde ; 2) GATA-1 est capable d’interagir avec la protéine du rétinoblastome pRb, impliquée dans la régulation du cycle cellulaire, et le complexe formé est nécessaire à l’érythropoïèse terminale.L'objectif de ma thèse était d’étudier les mécanismes moléculaires impliqués dans la balance prolifération/différenciation cellulaire au cours de l’érythropoïèse, et en particulier de déterminer le rôle moléculaire et physiologique de la phosphorylation de GATA-1 par Akt en réponse à l’Epo. Nos travaux ont montré que cette phosphorylation est une des clefs de la dynamique de l’érythropoïèse. Dans sa forme non phosphorylée, GATA-1 ralentit le cycle cellulaire via le complexe GATA-1/pRb/E2F. Cette étape préliminaire est nécessaire à la mise en place de la différenciation érythroïde terminale. La phosphorylation de GATA-1 induit d’une part la dissociation de GATA-1/pRb/E2F favorisant l’expansion cellulaire, et d’autre part la formation du complexe GATA-1/FOG-1 nécessaire à l’activation des gènes érythroïdes. Ce modèle apporte une explication moléculaire au blocage de la différenciation érythroïde terminale induite par le mutant GATA-1V205G qui n’interagit pas avec FOG-1. Ainsi, la phosphorylation constitutive de GATA-1V205G et l’augmentation de la quantité relative de FOG-1 permettent de restaurer la différenciation érythroïde induite par ce mutant in vitro. Enfin, l’étude d’un modèle murin exprimant une protéine GATA-1 non phosphorylable par Akt montre l’apparition d’une anémie létale lorsque la voie IGF-1 est inhibée. Cela démontre l’importance de la dynamique moléculaire induite par la phosphorylation de GATA-1, et met en évidence le rôle majeur de l’IGF-1 dans l’érythropoïèse in vivo.En conclusion, nous proposons un nouveau modèle moléculaire de la régulation de la balance prolifération/différenciation érythroïde dans lequel la phosphorylation de GATA-1 par Akt coordonne la distribution de GATA-1 dans deux complexes protéiques fonctionnels différents : GATA-1/pRb/E2F versus GATA-1/FOG-1. Nous mettons également en évidence l’IGF-1 comme acteur central de la compensation mise en place in vivo pour pallier à l’absence de phosphorylation de GATA-1With more than 100 billion red blood cells generated every day, the erythroid lineage has the largest output of cell production in adult mammals. This production requires a tight balance between cell proliferation, mainly controlled by erythropoietin (Epo)/PI3K/Akt signaling pathway, and erythroid differentiation induced by GATA-1 and FOG-1 transcription factors. Various links between these two processes have been previously demonstrated in the laboratory: 1) Epo-activated Akt directly phosphorylates GATA-1 transcription factors, and this phosphorylation seems to be involved in erythroid differentiation; 2) GATA-1 binds to the cell cycle regulator retinoblastoma protein (pRb), and the resulting complex is essential for terminal erythropoiesis.We investigated the molecular mechanisms involved in the cell proliferation/differentiation balance during terminal erythropoiesis; in particular, we studied the molecular and physiological role of Epo-induced GATA-1 phosphorylation. Our findings suggest that this phosphorylation is one of the key processes in erythropoiesis dynamics. In its unphosphorylated form, GATA-1 can break cell cycle progression via GATA-1/pRb/E2F complex. This preliminary step is necessary for terminal erythroid differentiation. GATA-1 phosphorylation promotes GATA-1/pRb/E2F dissociation, allowing cell cycle progression, and GATA-1/FOG-1 binding, necessary to activate erythroid genes. Our model provides a molecular explanation for the arrest of terminal erythroid differentiation observed in the non-FOG-1-binding mutant GATA-1V205G. We show that the constitutive phosphorylation of GATA-1V205G and the increase of FOG-1 protein amount rescue erythroid differentiation in vitro. Finally, knock-in expression of unphosphorylatable GATA-1 in mice leads to lethal anemia when the IGF-1 signaling pathway is inhibited. This shows the importance of the molecular dynamics of GATA-1 phosphorylation, and highlights the major role of IGF-1 in erythropoiesis, in vivo.In conclusion, we propose a new molecular model for the control of the balance between proliferation and erythroid differentiation. GATA-1 phosphorylation by Akt coordinates the involvement of GATA-1 in two different functional protein complexes: GATA-1/pRb/E2F and GATA-1/FOG-1. We also highlight the major role of IGF-1 in compensating for the lack of GATA-1 phosphorylation in vivo
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Conley, Travis B. "The influence of training status on ERK and AKT phosphorylation in human skeletal muscle." Virtual Press, 2005. http://liblink.bsu.edu/uhtbin/catkey/1319219.
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Exercise induces morphological and metabolic adaptations that are highly specific to the mode of exercise training. These specific phenotypical changes are due to an equally specific molecular response that may depend on the activation and coordination intramuscular signaling pathways. Just as metabolic and morphological changes are influenced by the mode of exercise training, the signaling pathways that mediate exercise adaptation may also be directly related to the training status of skeletal muscle. For example, pre-conditioned skeletal muscle may exhibit a specific intracellular signaling response to an acute bout of exercise that is dependent on past training history. Both Akt (protein kinase B) and extra-cellular signal-related kinase (ERK 1 /2) have been shown to be phosphorylated in response to an acute bout of resistance exercise in human skeletal muscle and have been suggested to mediate the adaptive response to exercise. The purpose of this investigation was to examine the response of Akt and ERKI/2 to an acute bout of resistance exercise in three groups with distinctly different exercise training backgrounds. Twenty one subjects performed 3 sets of 10 repetitions of knee extension exercise at 70% 1-RM. The subjects consisted of a resistance-trained group (RE) (n=7), endurance trained group (END) (n=7) and a sedentary group (SED) (n=7). Muscle biopsies were taken from the vastus lateralis muscle before, immediately after, and 10 min post-exercise and were analyzed for phosphorylation of Akt and ERK1/2. ERK1/2 phosphorylation increased 47%, and 54% from pre-exercise to immediately post-exercise in the SED and RE groups respectively (p < 0.05). ERK1/2 phosphorylation increased 95%, 196%, and 47% from pre-exercise to 10 min post-exercise in the SED, RE, and END groups, respectively. (p < 0.05). The magnitude of ERK1/2 phosphorylation 10 min post-exercise was different between each group and may be linked to the group's training status. (p < 0.05) Akt phosphorylation decreased 42% and 37% from pre-exercise to immediately post-exercise in the SED and END group, respectively (p < 0.05). There was a 40 % increase in Akt phosphorylation from immediate post-exercise to 10 min post-exercise in the END group. In conclusion, training status appears to influence the magnitude and time course of activation of both Akt and ERK1/2 in response to an acute bout of resistance exercise. The immediate response of both ERK1/2 and Akt may play a key role in the adaptive response of skeletal muscle ultimately resulting in metabolic and morphological changes that are dependent on the past training history of the individual.School of Physical Education, Sport, and Exercise Science
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Lyons, Traci Renae. "Analysis of potential substrates for the pro-survival kinase AKT /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2006.
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Thesis (Ph.D. in Molecular Biology) -- University of Colorado at Denver and Health Sciences Center, 2006.Typescript. Includes bibliographical references (leaves 194-209). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;
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Chopra, Ines. "Molecular Mechanisms of AMPK- and Akt-Dependent Survival of Glucose-Starved Cardiac Myocytes." Scholarly Repository, 2012. http://scholarlyrepository.miami.edu/oa_dissertations/710.
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Muscle may experience hypoglycemia during ischemia or insulin infusion. During severe hypoglycemia energy production is blocked and an increase in AMP:ATP activates the energy sensor and putative insulin-sensitizer AMP-dependent protein kinase (AMPK). AMPK promotes energy conservation and survival by shutting down anabolism and activating catabolic pathways. We investigated the molecular mechanism of a unique glucose stress defense pathway involving AMPK-dependent, insulin-independent activation of the insulin signaling pathway. Results from my work showed that the central insulin signaling pathway is rapidly activated when cardiac and skeletal myocytes are subjected to conditions of glucose starvation. The effect occurred independently of insulin receptor ligands (insulin and IGF-1). There was a >10-fold increase in the activity of Akt as determined by phosphorylation on both Thr308 and Ser473. Phosphorylation of glycogen synthase 3 beta (GSK3b) increased in parallel, but phosphorylation of ribosomal 70S subunit-S6 protein kinase (S6K) and the mammalian target of rapamycin complex 1 (mTORC1) decreased. We identified AMPK as an intermediate in this signaling network; AMPK was activated by glucose starvation and many of the effects were mimicked by the AMPK-selective activator aminoimidazole carboxamide ribonucleotide (AICAR) and blocked by AMPK inhibitors. Glucose starvation increased the phosphorylation on IRS-1 on Ser789, but phosphomimetics revealed that this conferred negative regulation. Glucose starvation enhanced tyrosine phosphorylation of IRS-1 and the insulin receptor, effects that were blocked by AMPK inhibition and mimicked by AICAR. In vitro kinase assays using purified proteins confirmed that the insulin receptor is a direct target of AMPK. Insulin receptor kinase activity was essential for cardiac myocytes to survive gluose starvation as inhibition of the IR led to increased cell death in glucose-starved myocytes. Selective activation of mTORC2 by glucose starvation to increase Akt-Ser473 phosphorylation was dependent on the presence of rictor. SIN1 also seemed to be instrumental in the activation of mTORC2 as its levels and binding to rictor increased under glucose starvation. AMPK-mediated activation of the insulin signaling pathway conferred significant protection against the stresses of glucose starvation. Glucose starvation promoted energy conservation, augmented glucose uptake and enhanced insulin sensitivity in an AMPK- and Akt-dependent manner. My results describe a novel ligand-independent and AMPK-dependent activation of the insulin signaling pathway via direct phosphorylation and activation of the IR followed by activation of PI3K and Akt. These results may be relevant in conditions of myocardial ischemia superimposed with type 2 diabetes where AMPK could directly modify the IR to promote cell survival and confer protection.
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Goodwani, Sunil G. "Amoxicillin and Augmentin Reduce Ethanol Intake and Increase GLT1 Expression as well as AKT Phosphorylation in Mesocorticolimbic Regions." University of Toledo Health Science Campus / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=mco1403873055.
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Tamburini-Bonnefoy, Jérôme. "Régulation des voies de signalisation P13K/Akt et mTOR dans les leucémies aiguës myéloïdes : implications physiopathologiques et thérapeutiques." Paris 7, 2009. http://www.theses.fr/2009PA077179.
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Nous avons montré qu'une activation constitutive de la voie PBK/Akt est détectée dans 50% des _ leucémies aiguës myéloïdes (LAM), due le plus souvent à une autocrinie IGF-1/IGF-1R. Néanmoins, l'inhibition spécifique de la PI3K ou de l'IGFlR n'est que cytostatique dans les LAM. L'inhibition spécifique de mTORCl par la rapamycine induit une sur-stimulation de la voie PI3K/Akt dépendante l'IGFl. Ce mécanisme limite l'activité anti-leucémique de la rapamycine dans les LAM. Nous avons ensuite montré que mTORCl ne contrôle pas la traduction dans les LAM. La rapamycine ne réprime donc pas la synthèse de protéines oncogéniques expliquant ses effets limités dans les LAM. Ce mécanisme dépend de la kinase Pim-2, qui contrôle la phosphorylation du régulateur traductionnel 4E-BP1, suggérant l'intérêt potentiel d'inhibiteurs de Pim-2 dans les LAM. De plus, l'inhibition du complexe d'initiation de la traduction par le 4EGI-1 induit l'apoptose des blastes de LAM sans toxicité sur les cellules hématopoïétiques normales, désignant l'inhibition de la traduction comme une nouvelle perspective thérapeutiques dans les LAM. Nous avons ensuite montré que mTOR contrôle 4E-BP1 et ainsi la traduction dans les LAM, indépendamment des complexes mTORCl et mTORC2. Nous avons activé le répresseur physiologique de mTOR, la voie LKB1/AMPK, par la metformine, ce qui se traduit par des effets anti-leucémiques marqués dans les LAM. Ce travail a donc contribué à décrire la dérégulation oncogénique de la traduction comme étant une cible intéressante pour le développement de thérapeutiques — ciblées, par diverses approches basées sur une meilleure compréhension de la physiopathologie des LAMIn acute myeloid leukemia (AML), aberrant activation of signal transduction pathways enhances the survival of leukemic cells. We showed that 50% of primary AML samples had a constitutive activation of -PI3K/Akt generally due to an autocrine IGF-1/IGF-1R loop. However, specific PI3K and ÏGF-1R inhibitors'only showed limited anti-leukemic activity. The specific inhibition of mTORCl by rapamycm induced an IGF 1-dependent overactivation of PI3K that limited thé anti-leukemic potential of rapamycm. This emphasized the potential benefit of dual PI3K and mTORCl inhibitors in AML. Surprismgly, the mRNA translation process was not controlled by mTORCl in AML, and rapamycm failed to reduce the expression of oncogenic proteins. The Pim-2 kinase was involved in this mechamsm suggesting a potential benefit for Pim-2 inhibitors in the future. We showed that directly targeting the translation initiating complex by the 4EGI-1 compound decreased AML cell survival while sparing normal hematopoiesis, suggesting other therapeutic perspectives in AML therapy. We also showed that mTOR controlled by complex phosphorylation events the translation regulator 4E-BP1 m AML, independently of mTORCl and mTORC2 Finally, we activated the LKB1/AMPK pathway using metformin, which represents a physiological repressor of mTOR activity. This molecule markedly impaired the translation of oncogenic mRNA and repressed the growth of AML cells. The present work therefore contributed to emphasize the oncogenic deregulation of mRNA translation as a valuable target m AML that could be inhibited using different physiologic-based approaches
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Lyros, Orestis, Ann-Kristin Lamprecht, Linghui Nie, René Thieme, Katharina Götzel, Mario Gasparri, George Haasler, Parvaneh Rafiee, Reza Shaker, and Ines Gockel. "Dickkopf-1 (DKK1) promotes tumor growth via Akt-phosphorylation and independently of Wnt-axis in Barrett’s associated esophageal adenocarcinoma." e-Century Publishing, 2019. https://ul.qucosa.de/id/qucosa%3A33709.
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Esophageal adenocarcinoma (EAC) is still associated with poor prognosis, despite modern multi-modal therapies. New molecular markers, which control cell cycle and promote lymph node metastases or tumor growth, may introduce novel target therapies. Dickkopf-1 (DKK1) is a secreted glycoprotein that blocks the oncogenic Wnt/β-catenin signaling and its aberrant expression has been observed in many malignancies, including EAC. In this study, we investigated the biological role of DKK1 in EAC. Analysis of DKK1 and active β-catenin expression in human esophageal tissues confirmed a simultaneous DKK1-overexpression together with aberrant activation of β-catenin signaling in EAC in comparison with Barrett’s and healthy mucosa. To elucidate the molecular role of DKK1, the OE33 adenocarcinoma cells, which were found to overexpress DKK1, were subjected to functional and molecular assays following siRNA-mediated DKK1-knockdown. At the functional level, OE33 cell viability, proliferation, migration and invasion were significantly attenuated by the absence of DKK1. At the molecular level, neither DKK1-knockdown nor application of exogenous recombinant DKK1 were found to alter the baseline β-catenin signaling in OE33 cells. However, DKK1-knockdown significantly abrogated downstream Akt-phosphorylation. On the other hand, the Wnt-agonist, Wnt3a, restored the Akt-phorphorylation in the absence of DKK1, without, however, being able to further stimulate β-catenin transcription. These findings suggest that the β-catenin transcriptional activity in EAC is independent of Wnt3a/DKK1 site-of-action and define an oncogenic function for DKK1 in this type of malignancy via distinct activation of Akt-mediated intracellular pathways and independently of Wnt-axis inhibition. Taken together, DKK1 may present a novel therapeutic target in EAC.
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Murakami, Tomoaki. "Angiopoietin-1 attenuates H2O2-induced SEK1/JNK phosphorylation through the phosphatidylinositol 3-kinase/Akt pathway in vascular endothelial cells." Kyoto University, 2006. http://hdl.handle.net/2433/143830.
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Matthews, Jason Aaron. "Investigation of the effects of increased levels of O-GlcNAc protein modification on protein kinase C and Akt." [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001723.
Full textBooks on the topic "AKT PHOSPHORYLATION"
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Beninger, Richard J. Life's rewards. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198824091.001.0001.
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Life’s Rewards: Linking Dopamine, Incentive Learning, Schizophrenia, and the Mind explains how increased brain dopamine produces reward-related incentive learning, the acquisition by neutral stimuli of increased ability to elicit approach and other responses. Dopamine decreases may produce inverse incentive learning, the loss by stimuli of the ability to elicit approach and other responses. Incentive learning is gradually lost when dopamine receptors are blocked. The brain has multiple memory systems defined as “declarative” and “non-declarative;” incentive learning produces one form of non-declarative memory. People with schizophrenia have hyperdopaminergia, possibly producing excessive incentive learning. Delusions may rely on declarative memory to interpret the world as it appears with excessive incentive learning. Parkinson’s disease, associated with dopamine loss, may involve a loss of incentive learning and increased inverse incentive learning. Drugs of abuse activate dopaminergic neurotransmission, leading to incentive learning about drug-associated stimuli. After withdrawal symptoms have been alleviated by detoxification treatment, drug-associated conditioned incentive stimuli will retain their ability to elicit responses until they are repeatedly experienced in the absence of primary drug rewards. Incentive learning may involve the action of dopamine at dendritic spines of striatal medium spiny neurons that have recently had glutamatergic input from assemblies of cortical neurons activated by environmental and proprioceptive stimuli. Glutamate initiates a wave of phosphorylation normally followed by a wave of phosphatase activity. If dopaminergic neurons fire, stimulation of D1 receptors prolongs the wave of phosphorylation, allowing glutamate synaptic strengthening. Activity in dopaminergic neurons in humans appears to affect mental experience.
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Jancura, Daniel, and Erik Sedlák. Bioenergetika. Univerzita Pavla Jozefa Šafárika, Vydavateľstvo ŠafárikPress, 2021. http://dx.doi.org/10.33542/be2021-0022-6.
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Prekladaný vysokoškolský učebný text „Bioenergetika“ by mal slúžiť ako úvod do problematiky štúdia v oblasti bioenergetiky. Táto vedná oblast je v súčasnosti vysoko aktuálna, pretože výsledky získané bioenergetickým výskumom v uplynulých rokoch zreteľne ukazujú, že bioenergetické procesy prebiehajúce v živých systémoch neslúžia “len” na transformáciu energie, ale ovplyvňujú aj priebeh procesov ako sú apoptóza, starnutie, vznik a rozvoj mnohých ochorení (predovšetkým neurodegeneratívnych). Tieto skutočnosti jednoznačne naznačujú potrebu existencie kvalitných učebných textov, ktoré by prijateľným spôsobom umožnili študentom získať potrebné informácie a vedomosti v tejto vednej discipline. Z vyššie uvedených dôvodov sme sa rozhodli vytvoriť tieto učebné texty, ktoré sú vo forme desiatich samostatných kapitol, ktoré však na seba prirodzene a logicky nadväzujú. Jedna kapitola predstavuje v podstate jednu prednášku v rámci kurzu Bioenergetiky, ktorý je realizovaný na Prírodovedeckej fakulte Univerzity Pavla Jozefa Šafárika v Košiciach na magisterskom a doktorandskom stupni študijného programu „Biofyzika“. Zároveň tieto texty môžu poslúžiť aj pri výučbe v študijnom predmete Biochémia, ktorý je prednášaný v bakalárskych a magisterských stupňoch študijných programov “Biochémia” resp. “Biofyzika”. Dovoľujeme si vyjadriť presvedčenie, že tieto učebné texty by mohli byť istým spôsobom nápomocné aj vedeckým pracovníkom pracujúcim v oblasti výskumu týkajúcho sa problematiky transformáci energie v biologických organizmoch a fenoménoch spojených s touto transformáciou. V týchto učebných textoch sú postupne uvádzané poznatky týkajúce sa základných konceptov bioenergetiky, mechanizmov procesov ako sú glykolýza a Krebsov cyklus (okrem podrobného a uceleného popis týchto procesov je tu uvedený aj všeobecný náhľad o prepojenosti týchto procesov ako aj ich začlenenie do kompaktného pohľadu na celkový proces transformácie energie v biologických organizmoch), zloženia štruktúry a funkčnosti biologických membrán (táto oblast je nevyhnutná pre lepšie pochopenie poznatkov, ktoré sú uvedené v nasledujúcich kapitolách). V nasledujúcich kapitolách sa učebný text zaoberá popisom štruktúry a funkcie mitochondrií, pričom veľký dôraz je dávaný na popis vlastností a mechanizmov fungovania štyroch komplexov dýchacieho reťazca a ATP-syntázy. Tieto komplexy vytvárajú podmienky pre existenciu “najdôležitejšieho” bioenergetického procesu, oxidatívnej fosforylácie. V záverečných dvoch kapitolách sú uvedené mechanizmy procesov vytvárajúcich fotosyntézu, jej svetlej aj tmavej fázy. Sú tu relevantné informácie o tomto “druhom” najdôležitejšom bioenergetickom procese prebiehajúcom v mnohých biologických organizmoch a poskytujúcom možnosť transformácie enrgie elektromagnetického žiarenia na energiu “ukrytú” v chemických väzbách určitých chemických molekúl. Chceme vyjadriť naše presvedčenie, že predložené učebné texty “Bioenergetika” budú dobrým “pomocníkom a inšpirátorom” pre mnohých študentov, ktorí sa budú chcieť dozvedieť čo najviac o fascinujúcich štruktúrach a mechanizmoch umožňujúcich transformáciu energie v živých systémoch, bez ktorej by nebola možná existencia života ako ho poznáme. Želáme príjemné a podnetné čítanie a štúdium. URL: www.unibook.upjs.sk The textbook "Bioenergetics" should serve as an introduction to the study of bioenergetics. This field of science is currently highly actual, as the results of the bioenergetics research in recent years clearly show that bioenergetics processes in living systems can "serve" not only to transformation of energy, but also affect the course of processes such as apoptosis, aging, origin and development of many diseases (especially neurodegenerative). These facts clearly indicate the need for the existence of quality teaching texts that would allow students to acquire the necessary information and knowledge in this scientific discipline in an acceptable way. For the above mentioned reasons, we decided to create these textbooks, which are in the form of ten chapters, which naturally and logically follow each other. One chapter basically presents one lecture within the course of Bioenergetics, which is realized at the Faculty of Science of the Pavel Jozef Šafárik University in Košice at the master's and doctoral degree of the study program "Biophysics". At the same time, these texts can also be used for teaching in the study subject Biochemistry, which is taught in the bachelor's and master's degree programs of the study programs "Biochemistry" resp. “Biophysics”. We would like to express our conviction that these textbooks could in some way also help researchers working in the field of the energy transformation in biological organisms and the phenomena associated with this transformation. These textbooks present knowledge about the basic concepts of bioenergetics, the mechanisms of processes such as glycolysis and the Krebs cycle (in addition to a detailed and comprehensive description of these processes, there is also a general view of the interconnectedness of these processes and their incorporation into a compact view of the overall energy transformation in biological organisms), the structure and functionality of biological membranes (this area is necessary for a better understanding of the knowledge presented in the following chapters). In the following chapters, the textbook deals with the description of the structure and function of mitochondria, with great emphasis on the properties and mechanisms of functioning of the four complexes of the respiratory chain and ATP-synthase. These complexes create the basis for the existence of the "most important" process in bioenergetics, oxidative phosphorylation. In the final two chapters, the mechanisms of the processes that produce photosynthesis, its light and dark phases, are presented. There is relevant information about this "second" most important bioenergetics process taking place in many biological organisms and providing the possibility of transforming the energy of electromagnetic radiation into energy "hidden" in the chemical bonds of certain chemical molecules. We want to express our conviction that the textbooks "Bioenergetics" will be a good "helper and inspirer" for many students who want to learn as much as possible about the fascinating structures and mechanisms for energy transformation in living systems, without which it would not be possible existence of life as we know it.
Book chapters on the topic "AKT PHOSPHORYLATION"
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Hirai, K., T. Hayashi, P. H. Chan, V. J. Basus, T. L. James, and Lawrence Litt. "Akt phosphorylation and cell survival after hypoxia-induced cytochrome c release in superfused respiring neonatal rat cerebrocortical slices." In Brain Edema XII, 227–30. Vienna: Springer Vienna, 2003. http://dx.doi.org/10.1007/978-3-7091-0651-8_49.
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Appuhamy, J. A. D. R. N., and M. D. Hanigan. "Modeling the effects of insulin and amino acids on the phosphorylation of mTOR, Akt, and 4EBP1 in mammary cells." In Modelling nutrient digestion and utilisation in farm animals, 225–32. Wageningen: Wageningen Academic Publishers, 2011. http://dx.doi.org/10.3920/978-90-8686-712-7_25.
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Pirincci Ercan, Deniz, and Frank Uhlmann. "Analysis of Cell Cycle Progression in the Budding Yeast S. cerevisiae." In Methods in Molecular Biology, 265–76. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1538-6_19.
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AbstractThe cell cycle is an ordered series of events by which cells grow and divide to give rise to two daughter cells. In eukaryotes, cyclin–cyclin-dependent kinase (cyclin–Cdk) complexes act as master regulators of the cell division cycle by phosphorylating numerous substrates. Their activity and expression profiles are regulated in time. The budding yeast S. cerevisiae was one of the pioneering model organisms to study the cell cycle. Its genetic amenability continues to make it a favorite model to decipher the principles of how changes in cyclin-Cdk activity translate into the intricate sequence of substrate phosphorylation events that govern the cell cycle. In this chapter, we introduce robust and straightforward methods to analyze cell cycle progression in S. cerevisiae. These techniques can be utilized to describe cell cycle events and to address the effects of perturbations on accurate and timely cell cycle progression.
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Pu, Jing, and Pingsheng Liu. "Fatty Acids Stimulate Glucose Uptake by the PI3K/AMPK/Akt and PI3K/ERK1/2 Pathways." In Protein Phosphorylation in Human Health. InTech, 2012. http://dx.doi.org/10.5772/52456.
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Yildiz, Aysegul, and Yesim Kaya. "Post-Translational Regulation of the Activity of ERK/MAPK and PI3K/AKT Signaling Pathways in Neuroblastoma Cancer." In Post-Translational Modifications in Cellular Functions and Diseases [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.96176.
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Pathogenesis of cancer is a multi-step process containing a number of cellular alterations such as post-translational dysregulation of intracellular signaling proteins. These alterations control several functions in carcinogenesis such as angiogenesis, metastasis, evading growth suppressors, and sustaining proliferative signaling. Data of various studies has demonstrated that Phosphatidylinositol 3-kinase (PI3K/AKT) and Mitogen-activated protein kinase (ERK/MAPK) pathways are both abnormally activated in many cancer types, including neuroblastoma. ERK/MAPK and PI3K/AKT signaling pathways that are regulated by sequential phosphorylation upon extracellular stimulation have many important functions in cell cycle, migration, proliferation and apoptosis. Besides their aberrant phosphorylation/activation, there is a crosstalk between these two pathways resulting in an anti-apoptotic effect. In this chapter, carcinogenetic abnormalities in post-translational regulation of the activity of ERK/MAPK and PI3K/AKT pathways in neuroblastoma and other cancers will be summarized. In addition, several crosstalk nodes between two pathways will be briefly explained. All these concepts are not only crucial for thoroughly understanding the molecular basis of carcinogenesis but also choosing the appropriate molecular targets for effective diagnosis and treatment.
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Ning, Junyu, and David R. Clemmons. "IGF-I Suppresses AMPK Activity through Stimulation of Akt Mediated Phosphorylation of AMPK at S485." In The Endocrine Society's 92nd Annual Meeting, June 19–22, 2010 - San Diego, P1–137—P1–137. Endocrine Society, 2010. http://dx.doi.org/10.1210/endo-meetings.2010.part1.p3.p1-137.
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Berrou, Mohammed, Basel Taha, Alemu Fite, Nabanita S. Datta, and Abdul B. Abou-Samra. "Globular Adiponectin Increases the Phosphorylation of AKT, ERK1/2 and CREB in MC3T3-E1 Cells, Affecting Their Proliferation, Gene Expression and Glucose Uptake." In BASIC - Bone, Calciotropic Hormones & Vitamin D, P1–186—P1–186. The Endocrine Society, 2011. http://dx.doi.org/10.1210/endo-meetings.2011.part1.p9.p1-186.
Full textConference papers on the topic "AKT PHOSPHORYLATION"
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Adi, Y. A., F. Adi-Kusumo, L. Aryati, and M. S. Hardianti. "Modelling inhibition of AKT phosphorylation in acute myeloid leukemia." In THE 2016 CONFERENCE ON FUNDAMENTAL AND APPLIED SCIENCE FOR ADVANCED TECHNOLOGY (CONFAST 2016): Proceeding of ConFAST 2016 Conference Series: International Conference on Physics and Applied Physics Research (ICPR 2016), International Conference on Industrial Biology (ICIBio 2016), and International Conference on Information System and Applied Mathematics (ICIAMath 2016). Author(s), 2016. http://dx.doi.org/10.1063/1.4953987.
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Adi, Y. A., F. A. Kusumo, L. Aryati, and M. S. Hardianti. "A mathematical model of phosphorylation AKT in Acute Myeloid Leukemia." In SYMPOSIUM ON BIOMATHEMATICS (SYMOMATH 2015). AIP Publishing LLC, 2016. http://dx.doi.org/10.1063/1.4945059.
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Koirala, Pratirodh, and Yin Yuan MO. "Abstract 155: LncRNA AK023948 promotes breast tumorigenesis by enhancing AKT phosphorylation." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-155.
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Ali, Amna, and Diane F. Matesic. "Abstract 4523: Chaetoglobosin K, a dual Akt and JNK inhibitor, modulates Akt phosphorylation in an mTORC2 independent manner." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-4523.
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Elshiekh, Duaa Ibnomer, Hadeel Hendawi, Aya Goul, Dina Awartan, Isra Marei, Christopher Triggle, and Haissam Abou Saleh. "Effect of Hyperglycemia on eNOS function in EPCs." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0215.
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Type 2 diabetes mullites (T2DM) results in different cardiovascular complications. The main cause of these complications is endothelial dysfunction, which affects the endothelium physiologically and pathologically. The chronic hyperglycemia introduced by T2DM impacts the pivotal enzyme endothelial nitric oxide synthase (eNOS) in terms of phosphorylation and dimerization, which initiates oxidative stress and reduces the bioavailability of the vasodilator nitric oxide. To overcome endothelial dysfunction, endothelial progenitor cells (EPCs) contribute to vascular repair due to their regenerative characteristics. The effects of hyperglycemia on EPCs are understudied. Thus, this study aims to investigate the effects of hyperglycemia on the eNOS/Akt signaling pathway and reactive oxygen species (ROS) formation. Cells were treated with normal glucose (NG, 5.5mM) and high glucose (HG, 25mM) media for 3 & 6 days, and the effect on eNOS and Akt phosphorylation were assessed using western blot. ROS was assessed using CellROX stain following 1 and 3 days of treatment. Results showed that both acute and chronic hyperglycemia showed a trend towards decrease in phosphorylation of eNOS and Akt. In addition, ROS formation was increased following 24hr compared to NG. Further investigations are needed to enhance the capability of BOECs to serve as therapeutic tools in T2DM.
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MacEwan, Melanie, Ismatun Swati, Suqing Xie, Olena Ardacheva, Codrin Iacob, Edward Shin, Augustine Moscatello, Stimson Schantz, Raj K. Tiwari, and Jan Geliebter. "Abstract 3921: Androgens stimulate phosphorylation of ERK and AKT in thyroid cancer cells." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-3921.
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Koromilas, Antonis E., Rajesh Kamindla, Andreas I. Papadakis, Urszula Kazimierczak, Philippos Peidis, Shuo Wang, Clara Tenkerian, et al. "Abstract C51: eIF2alpha phosphorylation determines cell susceptibility to oxidative stress via Akt activation." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-c51.
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Roldan, Diana Barea, Christoph Hartmann, Stefanie Hubich-Rau, Tim Beissert, Claudia Paret, Giuseppe Cagna, Christoph Rohde, Stefan Wöll, Ugur Sahin, and Ozlem Tureci. "Abstract 763: PLAC1 interacts with FGF7 and promotes phosphorylation of FGFR2 and AKT." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-763.
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Shou, J., KC Osborne, J. Gee, R. Nicholson, and R. Schiff. "Akt-dependent phosphorylation on AIB1 serine 967 contributes to breast cancer tamoxifen resistance." In CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/0008-5472.sabcs-3021.
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Thakur, Shreya, Charyguly Annageldiyev, Srinivasa Ramisetti, Trupti Patel, Saumya Iyer, Pavan Dhanyamraju, Shantu Amiin, Arun Sharma, David Claxton, and Arati Sharma. "Abstract 358: Inhibition of AKT phosphorylation in acute myeloid leukemia by ISC 4." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-358.
Full textReports on the topic "AKT PHOSPHORYLATION"
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Wang, Yanru, and Keqiang Ye. Akt Phosphorylation and PI (3, 4, 5) P3 Binding Coordinately Inhibit the Tumor Suppressive Activity of Merlin. Fort Belvoir, VA: Defense Technical Information Center, February 2010. http://dx.doi.org/10.21236/ada523196.
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Da Silva, Thiago. CDK2 Phosphorylation on Threonine39 by AKT and Its Implication on Cyclin Binding, Cellular Localization, and Cell Cycle Progression. Fort Belvoir, VA: Defense Technical Information Center, October 2007. http://dx.doi.org/10.21236/ada488284.
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Granot, David, Richard Amasino, and Avner Silber. Mutual effects of hexose phosphorylation enzymes and phosphorous on plant development. United States Department of Agriculture, January 2006. http://dx.doi.org/10.32747/2006.7587223.bard.
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Research objectives 1) Analyze the combined effects of hexose phosphorylation and P level in tomato and Arabidopsis plants 2) Analyze the combined effects of hexose phosphorylation and P level in pho1 and pho2 Arabidopsis mutants 3) Clone and analyze the PHO2 gene 4) Select Arabidopsis mutants resistant to high and low P 5) Analyze the Arabidopsis mutants and clone the corresponding genes 6) Survey wild tomato species for growth characteristics at various P levels Background to the topic Hexose phosphorylating enzymes, the first enzymes of sugar metabolism, regulate key processes in plants such as photosynthesis, growth, senescence and vascular transport. We have previously discovered that hexose phosphorylating enzymes might regulate these processes as a function of phosphorous (P) concentration, and might accelerate acquisition of P, one of the most limiting nutrients in the soil. These discoveries have opened new avenues to gain fundamental knowledge about the relationship between P, sugar phosphorylation and plant development. Since both hexose phosphorylating enzymes and P levels affect plant development, their interaction is of major importance for agriculture. Due to the acceleration of senescence caused by the combined effects of hexose phosphorylation and P concentration, traits affecting P uptake may have been lost in the course of cultivation in which fertilization with relatively high P (30 mg/L) are commonly used. We therefore intended to survey wild tomato species for high P-acquisition at low P soil levels. Genetic resources with high P-acquisition will serve not only to generate a segregating population to map the trait and clone the gene, but will also provide a means to follow the trait in classical breeding programs. This approach could potentially be applicable for other crops as well. Major conclusions, solutions, achievements Our results confirm the mutual effect of hexose phosphorylating enzymes and P level on plant development. Two major aspects of this mutual effect arose. One is related to P toxicity in which HXK seems to play a major role, and the second is related to the effect of HXK on P concentration in the plant. Using tomato plants we demonstrated that high HXK activity increased leaf P concentration, and induced P toxicity when leaf P concentration increases above a certain high level. These results further support our prediction that the desired trait of high-P acquisition might have been lost in the course of cultivation and might exist in wild species. Indeed, in a survey of wild species we identified tomato species that acquired P and performed better at low P (in the irrigation water) compared to the cultivated Lycopersicon esculentum species. The connection between hexose phosphorylation and P toxicity has also been shown with the P sensitive species VerticordiaplumosaL . in which P toxicity is manifested by accelerated senescence (Silber et al., 2003). In a previous work we uncovered the phenomenon of sugar induced cell death (SICD) in yeast cells. Subsequently we showed that SICD is dependent on the rate of hexose phosphorylation as determined by Arabidopsis thaliana hexokinase. In this study we have shown that hexokinase dependent SICD has many characteristics of programmed cell death (PCD) (Granot et al., 2003). High hexokinase activity accelerates senescence (a PCD process) of tomato plants, which is further enhanced by high P. Hence, hexokinase mediated PCD might be a general phenomena. Botrytis cinerea is a non-specific, necrotrophic pathogen that attacks many plant species, including tomato. Senescing leaves are particularly susceptible to B. cinerea infection and delaying leaf senescence might reduce this susceptibility. It has been suggested that B. cinerea’s mode of action may be based on induction of precocious senescence. Using tomato plants developed in the course of the preceding BARD grant (IS 2894-97) and characterized throughout this research (Swartzberg et al., 2006), we have shown that B. cinerea indeed induces senescence and is inhibited by autoregulated production of cytokinin (Swartzberg et al., submitted). To further determine how hexokinase mediates sugar effects we have analyzed tomato plants that express Arabidopsis HXK1 (AtHXK1) grown at different P levels in the irrigation water. We found that Arabidopsis hexokinase mediates sugar signalling in tomato plants independently of hexose phosphate (Kandel-Kfir et al., submitted). To study which hexokinase is involved in sugar sensing we searched and identified two additional HXK genes in tomato plants (Kandel-Kfir et al., 2006). Tomato plants have two different hexose phosphorylating enzymes; hexokinases (HXKs) that can phosphorylate either glucose or fructose, and fructokinases (FRKs) that specifically phosphorylate fructose. To complete the search for genes encoding hexose phosphorylating enzymes we identified a forth fructokinase gene (FRK) (German et al., 2004). The intracellular localization of the four tomato HXK and four FRK enzymes has been determined using GFP fusion analysis in tobacco protoplasts (Kandel-Kfir et al., 2006; Hilla-Weissler et al., 2006). One of the HXK isozymes and one of the FRK isozymes are located within plastids. The other three HXK isozymes are associated with the mitochondria while the other three FRK isozymes are dispersed in the cytosol. We concluded that HXK and FRK are spatially separated in plant cytoplasm and accordingly might play different metabolic and perhaps signalling roles. We have started to analyze the role of the various HXK and FRK genes in plant development. So far we found that LeFRK2 is required for xylem development (German et al., 2003). Irrigation with different P levels had no effect on the phenotype of LeFRK2 antisense plants. In the course of this research we developed a rapid method for the analysis of zygosity in transgenic plants (German et al., 2003).
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Gao, Daming, Hiroyuki Inuzuka, Alan Tseng, and Wenyi Wei. Investigating the Role of Akt1 in Prostate Cancer Development Through Phosphorylation-Dependent Regulation of Skp2 Stability and Oncogenic Function. Fort Belvoir, VA: Defense Technical Information Center, September 2010. http://dx.doi.org/10.21236/ada535175.
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Wei, Wenyi, Daming Gao, Hiroyuki Inuzuka, and Alan Tseng. Investigating the Role of Akt1 in Prostate Cancer Development through Phosphorylation-dependent Regulation of Skp2 Stability and Oncogenic Function. Fort Belvoir, VA: Defense Technical Information Center, September 2012. http://dx.doi.org/10.21236/ada566865.
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Chamovitz, Daniel A., and Xing-Wang Deng. Developmental Regulation and Light Signal Transduction in Plants: The Fus5 Subunit of the Cop9 Signalosome. United States Department of Agriculture, September 2003. http://dx.doi.org/10.32747/2003.7586531.bard.
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Plants adjust their growth and development in a manner optimal for the prevailing light conditions. The molecular mechanisms by which light signals are transduced and integrated with other environmental and developmental signals are an area of intense research. (Batschauer, 1999; Quail, 2002) One paradigm emerging from this work is the interconnectedness of discrete physiological responses at the biochemical level, for instance, between auxin and light signaling (Colon-Carmona et al., 2000; Schwechheimer and Deng, 2001; Tian and Reed, 1999) and between light signaling and plant pathogen interactions (Azevedo et al., 2002; Liu et al., 2002). The COP9 signalosome (CSN) protein complex has a central role in the light control of plant development. Arabidopsis mutants that lack this complex develop photomorphogenically even in the absence of light signals (reviewed in (Karniol and Chamovitz, 2000; Schwechheimer and Deng, 2001). Thus the CSN was hypothesized to be a master repressor of photomorphogenesis in darkness, and light acts to bypass or eliminate this repression. However, the CSN regulates more than just photomorphogenesis as all mutants lacking this complex die near the end of seedling development. Moreover, an essentially identical complex was subsequently discovered in animals and yeast, organisms whose development is not light responsive, exemplifying how plant science can lead the way to exciting discoveries in biomedical model species (Chamovitz and Deng, 1995; Freilich et al., 1999; Maytal-Kivity et al., 2002; Mundt et al., 1999; Seeger et al., 1998; Wei et al., 1998). Our long-term objective is to determine mechanistically how the CSN controls plant development. We previously that this complex contains eight subunits (Karniol et al., 1998; Serino et al., 1999) and that the 27 ilia subunit is encoded by the FUS5/CSN7 locus (Karniol et al., 1999). The CSN7 subunit also has a role extraneous to the COP9 signalosome, and differential kinase activity has been implicated in regulating CSN7 and the COP9 signalosome (Karniol et al., 1999). In the present research, we further analyzed CSN7, both in terms of interacting proteins and in terms of kinases that act on CSN7. Furthermore we completed our analysis of the CSN in Arabidopsis by analyzing the remaining subunits. Outline of Original Objectives and Subsequent Modifications The general goal of the proposed research was to study the CSN7 (FUS5) subunit of the COP9 signalosome. To this end we specifically intended to: 1. Identify the residues of CSN7 that are phosphorylated. 2. Monitor the phosphorylation of CSN7 under different environmental conditions and under different genetic backgrounds. 3. Generate transgenic plants with altered CSN7 phosphorylation sites. 4. Purify CSN7 kinase from cauliflower. 5. Clone the Arabidopsis cDNA encoding CSN7 kinase 6. Isolate and characterize additional CSN7 interacting proteins. 7. Characterize the interaction of CSN7 and the COP9 signalosome with the HY5-COP1 transcriptional complex. Throughout the course of the research, emphasis shifted from studying CSN7 phosphorylation (Goals 1-3), to studying the CSN7 kinase (Goal 4 and 5), an in depth analysis of CSN7 interactions (Goal 6), and the study of additional CSN subunits. Goal 7 was also abandoned as no data was found to support this interaction.
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Locy, Robert D., Hillel Fromm, Joe H. Cherry, and Narendra K. Singh. Regulation of Arabidopsis Glutamate Decarboxylase in Response to Heat Stress: Modulation of Enzyme Activity and Gene Expression. United States Department of Agriculture, January 2001. http://dx.doi.org/10.32747/2001.7575288.bard.
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Most plants accumulate the nonprotein amino acid, g-aminobutyric acid (GABA), in response to heat stress. GABA is made from glutamate in a reaction catalyzed by glutamate decarboxylase (GAD), an enzyme that has been shown by the Israeli PI to be a calmodulin (CaM) binding protein whose activity is regulated in vitro by calcium and CaM. In Arabidopsis there are at least 5 GAD genes, two isoforms of GAD, GAD1 and GAD2, are known to be expressed, both of which appear to be calmodulin-binding proteins. The role of GABA accumulation in stress tolerance remains unclear, and thus the objectives of the proposed work are intended to clarify the possible roles of GABA in stress tolerance by studying the factors which regulate the activity of GAD in vivo. Our intent was to demonstrate the factors that mediate the expression of GAD activity by analyzing the promoters of the GAD1 and GAD2 genes, to determine the role of stress induced calcium signaling in the regulation of GAD activity, to investigate the role of phosphorylation of the CaM-binding domain in the regulation of GAD activity, and to investigate whether ABA signaling could be involved in GAD regulation via the following set of original Project Objectives: 1. Construction of chimeric GAD1 and GAD2 promoter/reporter gene fusions and their utilization for determining cell-specific expression of GAD genes in Arabidopsis. 2. Utilizing transgenic plants harboring chimeric GAD1 promoter-luciferase constructs for isolating mutants in genes controlling GAD1 gene activation in response to heat shock. 3. Assess the role of Ca2+/CaM in the regulation of GAD activity in vivo in Arabidopsis. 4. Study the possible phosphorylation of GAD as a means of regulation of GAD activity. 5. Utilize ABA mutants of Arabidopsis to assess the involvement of this phytohormone in GAD activation by stress stimuli. The major conclusions of Objective 1 was that GAD1 was strongly expressed in the elongating region of the root, while GAD2 was mainly expressed along the phloem in both roots and shoots. In addition, GAD activity was found not to be transcriptionally regulated in response to heat stress. Subsequently, The Israeli side obtained a GAD1 knockout mutation, and in light of the objective 1 results it was determined that characterization of this knockout mutation would contribute more to the project than the proposed Objective 2. The major conclusion of Objective 3 is that heat-stress-induced changes in GAD activity can be explained by heat-stress-induced changes in cytosolic calcium levels. No evidence that GAD activity was transcriptionally or translationally regulated or that protein phosphorylation was involved in GAD regulation (objective 4) was obtained. Previously published data by others showing that in wheat roots ABA regulated GABA accumulation proved not to be the case in Arabidopsis (Objective 5). Consequently, we put the remaining effort in the project into the selection of mutants related to temperature adaptation and GABA utilization and attempting to characterize events resulting from GABA accumulation. A set of 3 heat sensitive mutants that appear to have GABA related mutations have been isolated and partially characterized, and a study linking GABA accumulation to growth stimulation and altered nitrate assimilation were conducted. By providing a better understanding of how GAD activity was and was not regulated in vivo, we have ruled out the use of certain genes for genetically engineering thermotolerance, and suggested other areas of endeavor related to the thrust of the project that may be more likely approaches to genetically engineering thermotolerance.
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Granot, David, Scott Holaday, and Randy D. Allen. Enhancing Cotton Fiber Elongation and Cellulose Synthesis by Manipulating Fructokinase Activity. United States Department of Agriculture, 2008. http://dx.doi.org/10.32747/2008.7613878.bard.
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a. Objectives (a) Identification and characterization of the cotton fiber FRKs; (b) Generating transgenic cotton plants overproducing either substrate inhibited tomato FRK or tomato FRK without substrate inhibition; (c) Generating transgenic cotton plants with RNAi suppression of fiber expressed FRKs; (d) Generating Arabidopsis plants that over express FRK1, FRK2, or both genes, as additional means to assess the contribution of FRK to cellulose synthesis and biomass production. b. Background to the topic: Cellulose synthesis and fiber elongation are dependent on sugar metabolism. Previous results suggested that FRKs (fructokinase enzymes that specifically phosphorylate fructose) are major players in sugar metabolism and cellulose synthesis. We therefore hypothesized that increasing fructose phosphorylation may enhance fiber elongation and cellulose synthesis in cotton plants. Accordinlgy, the objectives of this research were: c. Major conclusions and achievements: Two cotton FRKs expressed in fibers, GhFRK2 and GhFRK3, were cloned and characterized. We found that GhFRK2 enzyme is located in the cytosol and GhFRK3 is located within plastids. Both enzymes enable growth on fructose (but not on glucose) of hexose kinase deficient yeast strain, confirming the fructokinase activity of the cloned genes. RNAi constructs with each gene were prepared and sent to the US collaborator to generate cotton plants with RNAi suppression of these genes. To examine the effect of FRKs using Arabidopsis plants we generated transgenic plants expressing either LeFRK1 or LeFRK2 at high level. No visible phenotype has been observed. Yet, plants expressing both genes simultaneously are being created and will be tested. To test our hypothesis that increasing fructose phosphorylation may enhance fiber cellulose synthesis, we generated twenty independent transgenic cotton plant lines overexpressing Lycopersicon (Le) FRK1. Transgene expression was high in leaves and moderate in developing fiber, but enhanced FRK activity in fibers was inconsistent between experiments. Some lines exhibited a 9-11% enhancement of fiber length or strength, but only one line tested had consistent improvement in fiber strength that correlated with elevated FRK activity in the fibers. However, in one experiment, seed cotton mass was improved in all transgenic lines and correlated with enhanced FRK activity in fibers. When greenhouse plants were subjected to severe drought during flowering and boll development, no genotypic differences in fiber quality were noted. Seed cotton mass was improved for two transgenic lines but did not correlate with fiber FRK activity. We conclude that LeFRK1 over-expression in fibers has only a small effect on fiber quality, and any positive effects depend on optimum conditions. The improvement in productivity for greenhouse plants may have been due to better structural development of the water-conducting tissue (xylem) of the stem, since stem diameters were larger for some lines and the activity of FRK in the outer xylem greater than observed for wild-type plants. We are testing this idea and developing other transgenic cotton plants to understand the roles of FRK in fiber and xylem development. We see the potential to develop a cotton plant with improved stem strength and productivity under drought for windy, semi-arid regions where cotton is grown. d. Implications, scientific and agricultural: FRKs are probably bottle neck enzymes for biomass and wood synthesis and their increased expression has the potential to enhance wood and biomass production, not only in cotton plants but also in other feed and energy renewable plants.
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Delmer, Deborah P., and Prem S. Chourey. The Importance of the Enzyme Sucrose Synthase for Cell Wall Synthesis in Plants. United States Department of Agriculture, October 1994. http://dx.doi.org/10.32747/1994.7568771.bard.
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The goal of this work was to understand the role of the enzyme sucrose synthase (SuSy) in synthesis of cellulose and callose in plants. The work resulting from the this grant leads to a number of conclusions. SuSy clearly plays diverse roles in carbon metabolism. It can associate with the plasma membrane of cells undergoing rapid cellulose deposition, such as cotton fibers, developing maize endosperm, gravistimulated pulvini, and transfer cells of the cotton seed. It is also concentrated at sites of high callose deposition (tapetal cells; cell plates). When SuSy levels are lowered by mutation or by anti-sense technology, cell walls undergo degeneration (maize endosperm) and show reduced levels of cellulose (potato tubers). In sum, our evidence has very much strengthened the concept that SuSy does function in the plasma membrane to channel carbon from sucrose via UDP-glucose to glucan synthase complexes. Soluble SuSy also clearly plays a role in providing carbon for starch synthesis and respiration. Surprisingly, we found that the cotton seed is one unique case where SuSy apparently does not play a role in starch synthesis. Current evidence in sum suggests that no specific SuSy gene encodes the membrane-associated form, although in maize the SS 1 form of SuSy may be most important for cell wall synthesis in the early stages of endosperm development. Work is still in progress to determine what does control membrane localization - and the current evidence we have favors a role for Ca2+, and possibly also protein phosphorylation by differentially regulated protein kinases. Finally, we have discovered for the first time, a major new family of genes that encode the catalytic subunit of the cellulose synthase of plants - a result that has been widely cited and opens many new approaches for the study of this important plant function.
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Philosoph-Hadas, Sonia, Peter B. Kaufman, Shimon Meir, and Abraham H. Halevy. Inhibition of the Gravitropic Shoot Bending in Stored Cut Flowers Through Control of Their Graviperception: Involvement of the Cytoskeleton and Cytosolic Calcium. United States Department of Agriculture, December 2005. http://dx.doi.org/10.32747/2005.7586533.bard.
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Original objectives: The basic goal of the present project was to study the mechanism involved in shoot graviperception and early transduction, in order to determine the sequence of events operating in this process. This will enable to control the entire process of gravity-induced differential growth without affecting vertical growth processes essential for development. Thus, several new postulated interactions, operating at the perception and early transduction stages of the signaling cascade leading to auxin-mediated bending, were proposed to be examined in snapdragon spikes and oat shoot pulvini, according to the following research goals: 1) Establish the role of amyloplasts as gravireceptors in shoots; 2) Investigate gravity-induced changes in the integrity of shoot actin cytoskeleton (CK); 3) Study the cellular interactions among actin CK, statoliths and cell membranes (endoplasmic reticulum - ER, plasma membrane - PM) during shoot graviperception; 4) Examine mediation of graviperception by modulations of cytosolic calcium - [Ca2+]cyt, and other second messengers (protein phosphorylation, inositol 1,4,5-trisphosphate - IP3). Revisions: 1) Model system: in addition to snapdragon (Antirrhinum majus L.) spikes and oat (Avena sativa) shoot pulvini, the model system of maize (Zea mays) primary roots was targeted to confirm a more general mechanism for graviperception. 2) Research topic: brassinolide, which were not included in the original plan, were examined for their regulatory role in gravity perception and signal transduction in roots, in relation to auxin and ethylene. Background to the topic: The negative gravitropic response of shoots is a complex multi-step process that requires the participation of various cellular components acting in succession or in parallel. Most of the long-lasting studies regarding the link between graviperception and cellular components were focused mainly on roots, and there are relatively few reports on shoot graviperception. Our previous project has successfully characterized several key events occurring during shoot bending of cut flowers and oat pulvini, including amyloplast displacement, hormonal interactions and differential growth analysis. Based on this evidence, the present project has focused on studying the initial graviperception process in flowering stems and cereal shoots. Major conclusions and achievements: 1) The actin and not the microtubule (MT) CK is involved in the graviperception of snapdragon shoots. 2) Gravisensing, exhibited by amyloplast displacement, and early transduction events (auxin redistribution) in the gravitropic response of snapdragon spikes are mediated by the acto-myosin complex. 3) MTs are involved in stem directional growth, which occurs during gravitropism of cut snapdragon spikes, but they are not necessary for the gravity-induced differential growth. 4) The role of amyloplasts as gravisensors in the shoot endodermis was demonstrated for both plant systems. 5) A gravity-induced increase in IP.