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Relevant bibliographies by topics / Src homology 2 domain (SH2 domain)

Academic literature on the topic 'Src homology 2 domain (SH2 domain)'

Author: Grafiati

Published: 10 December 2022

Last updated: 28 January 2023

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Journal articles on the topic "Src homology 2 domain (SH2 domain)"

1

Tian, M., and G. S. Martin. "The role of the Src homology domains in morphological transformation by v-src." Molecular Biology of the Cell 8, no. 7 (July 1997): 1183–93. http://dx.doi.org/10.1091/mbc.8.7.1183.

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The Src homology (SH2 and SH3) domains of v-Src are required for transformation of Rat-2 cells and for wild-type (morphr) transformation of chicken embryo fibroblasts (CEFs). We report herein that the N-terminal domains of v-Src, when expressed in trans, cannot complement the transformation defect of a deletion mutant lacking the "unique," SH3, and SH2 regions. However, the same regions of Src can promote transformation when translocated to the C terminus of v-Src, although the transformation of CEFs is somewhat slower. We conclude that the SH3 and SH2 domains must be present in cis to the catalytic domain to promote transformation but that transformation is not dependent on the precise intramolecular location of these domains. In CEFSs and in Rat-2 cells, the expression of wild-type v-Src results in tyrosine phosphorylation of proteins that bind to the v-Src SH3 and SH2 domains in vitro; mutations in the SH2 or SH3 and SH2 domains prevent the phosphorylation of these proteins. These findings are most consistent with models in which the SH3 and SH2 domains of v-Src directly or indirectly target the catalytic domain to substrates involved in transformation. However, the N-terminal domains of v-Src can promote tyrosine phosphorylation of certain proteins, in particular p130Cas, even when expressed in the absence of the catalytic domain, indicating that the N-terminal domains of v-Src have effects that are independent of the catalytic domain.

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2

Koch, C. A., M. F. Moran, D. Anderson, X. Q. Liu, G. Mbamalu, and T. Pawson. "Multiple SH2-mediated interactions in v-src-transformed cells." Molecular and Cellular Biology 12, no. 3 (March 1992): 1366–74. http://dx.doi.org/10.1128/mcb.12.3.1366-1374.1992.

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The Src homology 2 (SH2) domain is a noncatalytic region which is conserved among a number of signaling and transforming proteins, including cytoplasmic protein-tyrosine kinases and Ras GTPase-activating protein (GAP). Genetic and biochemical data indicate that the SH2 domain of the p60v-src (v-Src) protein-tyrosine kinase is required for full v-src transforming activity and may direct the association of v-Src with specific tyrosine-phosphorylated proteins. To test the ability of the v-Src SH2 domain to mediate protein-protein interactions, v-Src polypeptides were expressed as fusion proteins in Escherichia coli. The bacterial v-Src SH2 domain bound a series of tyrosine-phosphorylated proteins in a lysate of v-src-transformed Rat-2 cells, including prominent species of 130 and 62 kDa (p130 and p62). The p130 and p62 tyrosine-phosphorylated proteins that complexed v-Src SH2 in vitro also associated with v-Src in v-src-transformed Rat-2 cells; this in vivo binding was dependent on the v-Src SH2 domain. In addition to binding soluble p62 and p130, the SH2 domains of v-Src, GAP, and v-Crk directly recognized these phosphotyrosine-containing proteins which had been previously denatured and immobilized on a filter. In addition, the SH2 domains of GAP and v-Crk bound to the GAP-associated protein p190 immobilized on a nitrocellulose membrane. These results show that SH2 domains bind directly to tyrosine-phosphorylated proteins and that the Src SH2 domain can bind phosphorylated targets of the v-Src kinase domain.(ABSTRACT TRUNCATED AT 250 WORDS)

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3

Koch, C. A., M. F. Moran, D. Anderson, X. Q. Liu, G. Mbamalu, and T. Pawson. "Multiple SH2-mediated interactions in v-src-transformed cells." Molecular and Cellular Biology 12, no. 3 (March 1992): 1366–74. http://dx.doi.org/10.1128/mcb.12.3.1366.

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The Src homology 2 (SH2) domain is a noncatalytic region which is conserved among a number of signaling and transforming proteins, including cytoplasmic protein-tyrosine kinases and Ras GTPase-activating protein (GAP). Genetic and biochemical data indicate that the SH2 domain of the p60v-src (v-Src) protein-tyrosine kinase is required for full v-src transforming activity and may direct the association of v-Src with specific tyrosine-phosphorylated proteins. To test the ability of the v-Src SH2 domain to mediate protein-protein interactions, v-Src polypeptides were expressed as fusion proteins in Escherichia coli. The bacterial v-Src SH2 domain bound a series of tyrosine-phosphorylated proteins in a lysate of v-src-transformed Rat-2 cells, including prominent species of 130 and 62 kDa (p130 and p62). The p130 and p62 tyrosine-phosphorylated proteins that complexed v-Src SH2 in vitro also associated with v-Src in v-src-transformed Rat-2 cells; this in vivo binding was dependent on the v-Src SH2 domain. In addition to binding soluble p62 and p130, the SH2 domains of v-Src, GAP, and v-Crk directly recognized these phosphotyrosine-containing proteins which had been previously denatured and immobilized on a filter. In addition, the SH2 domains of GAP and v-Crk bound to the GAP-associated protein p190 immobilized on a nitrocellulose membrane. These results show that SH2 domains bind directly to tyrosine-phosphorylated proteins and that the Src SH2 domain can bind phosphorylated targets of the v-Src kinase domain.(ABSTRACT TRUNCATED AT 250 WORDS)

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4

Song, X., X. Shang, T. Ju, R. Cerny, W. Niu, and J. Guo. "A photoactivatable Src homology 2 (SH2) domain." RSC Advances 6, no. 56 (2016): 51120–24. http://dx.doi.org/10.1039/c6ra06211c.

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Klippel, A., J. A. Escobedo, W. J. Fantl, and L. T. Williams. "The C-terminal SH2 domain of p85 accounts for the high affinity and specificity of the binding of phosphatidylinositol 3-kinase to phosphorylated platelet-derived growth factor beta receptor." Molecular and Cellular Biology 12, no. 4 (April 1992): 1451–59. http://dx.doi.org/10.1128/mcb.12.4.1451-1459.1992.

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Upon stimulation by its ligand, the platelet-derived growth factor (PDGF) receptor associates with the 85-kDa subunit of phosphatidylinositol (PI) 3-kinase. The 85-kDa protein (p85) contains two Src homology 2 (SH2) domains and one SH3 domain. To define the part of p85 that interacts with the PDGF receptor, a series of truncated p85 mutants was analyzed for association with immobilized PDGF receptor in vitro. We found that a fragment of p85 that contains a single Src homology domain, the C-terminal SH2 domain (SH2-C), was sufficient for directing the high-affinity interaction with the receptor. Half-maximal binding of SH2-C to the receptor was observed at an SH2-C concentration of 0.06 nM. SH2-C, like full-length p85, was able to distinguish between wild-type PDGF receptor and a mutant receptor lacking the PI 3-kinase binding site. An excess of SH2-C blocked binding of full-length p85 and PI 3-kinase to the receptor but did not interfere with the binding of two other SH2-containing proteins, phospholipase C-gamma and GTPase-activating protein. These results demonstrate that a region of p85 containing a single SH2 domain accounts both for the high affinity and specificity of binding of PI 3-kinase to the PDGF receptor.

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Klippel, A., J. A. Escobedo, W. J. Fantl, and L. T. Williams. "The C-terminal SH2 domain of p85 accounts for the high affinity and specificity of the binding of phosphatidylinositol 3-kinase to phosphorylated platelet-derived growth factor beta receptor." Molecular and Cellular Biology 12, no. 4 (April 1992): 1451–59. http://dx.doi.org/10.1128/mcb.12.4.1451.

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Upon stimulation by its ligand, the platelet-derived growth factor (PDGF) receptor associates with the 85-kDa subunit of phosphatidylinositol (PI) 3-kinase. The 85-kDa protein (p85) contains two Src homology 2 (SH2) domains and one SH3 domain. To define the part of p85 that interacts with the PDGF receptor, a series of truncated p85 mutants was analyzed for association with immobilized PDGF receptor in vitro. We found that a fragment of p85 that contains a single Src homology domain, the C-terminal SH2 domain (SH2-C), was sufficient for directing the high-affinity interaction with the receptor. Half-maximal binding of SH2-C to the receptor was observed at an SH2-C concentration of 0.06 nM. SH2-C, like full-length p85, was able to distinguish between wild-type PDGF receptor and a mutant receptor lacking the PI 3-kinase binding site. An excess of SH2-C blocked binding of full-length p85 and PI 3-kinase to the receptor but did not interfere with the binding of two other SH2-containing proteins, phospholipase C-gamma and GTPase-activating protein. These results demonstrate that a region of p85 containing a single SH2 domain accounts both for the high affinity and specificity of binding of PI 3-kinase to the PDGF receptor.

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Xing, Z., H. C. Chen, J. K. Nowlen, S. J. Taylor, D. Shalloway, and J. L. Guan. "Direct interaction of v-Src with the focal adhesion kinase mediated by the Src SH2 domain." Molecular Biology of the Cell 5, no. 4 (April 1994): 413–21. http://dx.doi.org/10.1091/mbc.5.4.413.

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The recently described focal adhesion kinase (FAK) has been implicated in signal transduction pathways initiated by cell adhesion receptor integrins and by neuropeptide growth factors. To examine the mechanisms by which FAK relays signals from the membrane to the cell interior, we carried out a series of experiments to detect potential FAK interactions with proteins containing Src homology 2 (SH2) domains that are important intracellular signaling molecules. Using v-Src-transformed NIH3T3 cells, we showed that FAK was present in the immune-complex precipitated by anti-Src antibody, suggesting potential interaction of FAK with v-Src in vivo. We also showed potentially direct interaction of FAK with v-Src in vivo using the yeast two-hybrid system. Using recombinant FAK expressed in insect cells and bacterial fusion proteins containing Src SH2 domains, we showed direct binding of FAK to the Src SH2 domain but not to the SH3 domain in vitro. A kinase-defective mutant of FAK, which is not autophosphorylated, did not interact with the Src SH2 domain under the same conditions, suggesting the involvement of the FAK autophosphorylation sites. Treatment of FAK with a protein-tyrosine phosphatase decreased its binding to the Src SH2 domain, whereas autophosphorylation in vitro increased its binding. These results confirm the importance of FAK autophosphorylation sites in its interaction with SH2 domain-containing proteins. Taken together, these results suggest that FAK may mediate signal transduction events initiated on the cell surface by kinase activation and autophosphorylation that result in its binding to other key intracellular signaling molecules.

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Bibbins, K. B., H. Boeuf, and H. E. Varmus. "Binding of the Src SH2 domain to phosphopeptides is determined by residues in both the SH2 domain and the phosphopeptides." Molecular and Cellular Biology 13, no. 12 (December 1993): 7278–87. http://dx.doi.org/10.1128/mcb.13.12.7278-7287.1993.

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Src homology 2 (SH2) domains are found in a variety of signaling proteins and bind phosphotyrosine-containing peptide sequences. To explore the binding properties of the SH2 domain of the Src protein kinase, we used immobilized phosphopeptides to bind purified glutathione S-transferase-Src SH2 fusion proteins. With this assay, as well as a free-peptide competition assay, we have estimated the affinities of the Src SH2 domain for various phosphopeptides relative to a Src SH2-phosphopeptide interaction whose Kd has been determined previously (YEEI-P; Kd = 4 nM). Two Src-derived phosphopeptides, one containing the regulatory C-terminal Tyr-527 and another containing the autophosphorylation site Tyr-416, bind the Src SH2 domain in a specific though low-affinity manner (with about 10(4)-lower affinity than the YEEI-P peptide). A platelet-derived growth factor receptor (PDGF-R) phosphopeptide containing Tyr-857 does not bind appreciably to the Src SH2 domain, suggesting it is not the PDGF-R binding site for Src as previously reported. However, another PDGF-R-derived phosphopeptide containing Tyr-751 does bind the Src SH2 domain (with an affinity approximately 2 orders of magnitude lower than that of YEEI-P). All of the phosphopeptides which bind to the Src SH2 domain contain a glutamic acid at position -3 or -4 with respect to phosphotyrosine; changing this residue to alanine greatly diminishes binding. We have also tested Src SH2 mutants for their binding properties and have interpreted our results in light of the recent crystal structure solution for the Src SH2 domain. Mutations in various conserved and nonconserved residues (R155A, R155K, N198E, H201R, and H201L) cause slight reductions in binding, while two mutations cause severe reductions. The W148E mutant domain, which alters the invariant tryptophan that marks the N-terminal border of the SH2 domain, binds poorly to phosphopeptides. Inclusion of the SH3 domain in the fusion protein partially restores the binding by the W148E mutant. A change in the invariant arginine that coordinates twice with phosphotyrosine in the peptide (R175L) results in a nearly complete loss of binding. The R175L mutant does display high affinity for the PDGF-R peptide containing Tyr-751, via an interaction that is at least partly phosphotyrosine independent. We have used this interaction to show that the R175L mutation also disrupts the intramolecular interaction between the Src SH2 domain and the phosphorylated C terminus within the context of the entire Src protein; thus, the binding properties observed for mutant domains in an in vitro assay appear to mimic those that occur in vivo.

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9

Bibbins, K. B., H. Boeuf, and H. E. Varmus. "Binding of the Src SH2 domain to phosphopeptides is determined by residues in both the SH2 domain and the phosphopeptides." Molecular and Cellular Biology 13, no. 12 (December 1993): 7278–87. http://dx.doi.org/10.1128/mcb.13.12.7278.

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Src homology 2 (SH2) domains are found in a variety of signaling proteins and bind phosphotyrosine-containing peptide sequences. To explore the binding properties of the SH2 domain of the Src protein kinase, we used immobilized phosphopeptides to bind purified glutathione S-transferase-Src SH2 fusion proteins. With this assay, as well as a free-peptide competition assay, we have estimated the affinities of the Src SH2 domain for various phosphopeptides relative to a Src SH2-phosphopeptide interaction whose Kd has been determined previously (YEEI-P; Kd = 4 nM). Two Src-derived phosphopeptides, one containing the regulatory C-terminal Tyr-527 and another containing the autophosphorylation site Tyr-416, bind the Src SH2 domain in a specific though low-affinity manner (with about 10(4)-lower affinity than the YEEI-P peptide). A platelet-derived growth factor receptor (PDGF-R) phosphopeptide containing Tyr-857 does not bind appreciably to the Src SH2 domain, suggesting it is not the PDGF-R binding site for Src as previously reported. However, another PDGF-R-derived phosphopeptide containing Tyr-751 does bind the Src SH2 domain (with an affinity approximately 2 orders of magnitude lower than that of YEEI-P). All of the phosphopeptides which bind to the Src SH2 domain contain a glutamic acid at position -3 or -4 with respect to phosphotyrosine; changing this residue to alanine greatly diminishes binding. We have also tested Src SH2 mutants for their binding properties and have interpreted our results in light of the recent crystal structure solution for the Src SH2 domain. Mutations in various conserved and nonconserved residues (R155A, R155K, N198E, H201R, and H201L) cause slight reductions in binding, while two mutations cause severe reductions. The W148E mutant domain, which alters the invariant tryptophan that marks the N-terminal border of the SH2 domain, binds poorly to phosphopeptides. Inclusion of the SH3 domain in the fusion protein partially restores the binding by the W148E mutant. A change in the invariant arginine that coordinates twice with phosphotyrosine in the peptide (R175L) results in a nearly complete loss of binding. The R175L mutant does display high affinity for the PDGF-R peptide containing Tyr-751, via an interaction that is at least partly phosphotyrosine independent. We have used this interaction to show that the R175L mutation also disrupts the intramolecular interaction between the Src SH2 domain and the phosphorylated C terminus within the context of the entire Src protein; thus, the binding properties observed for mutant domains in an in vitro assay appear to mimic those that occur in vivo.

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Songyang, Z., S. E. Shoelson, J. McGlade, P. Olivier, T. Pawson, X. R. Bustelo, M. Barbacid, H. Sabe, H. Hanafusa, and T. Yi. "Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav." Molecular and Cellular Biology 14, no. 4 (April 1994): 2777–85. http://dx.doi.org/10.1128/mcb.14.4.2777-2785.1994.

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Src homology 2 (SH2) domains provide specificity to intracellular signaling by binding to specific phosphotyrosine (phospho-Tyr)-containing sequences. We recently developed a technique using a degenerate phosphopeptide library to predict the specificity of individual SH2 domains (src family members, Abl, Nck, Sem5, phospholipase C-gamma, p85 subunit of phosphatidylinositol-3-kinase, and SHPTP2 (Z. Songyang, S. E. Shoelson, M. Chaudhuri, G. Gish, T. Pawson, W. G. Haser, F. King, T. Roberts, S. Ratnofsky, R. J. Lechleider, B. G. Neel, R. B. Birge, J. E. Fajardo, M. M. Chou, H. Hanafusa, B. Schaffhausen, and L. C. Cantley, Cell 72:767-778, 1993). We report here the optimal recognition motifs for SH2 domains from GRB-2, Drk, Csk, Vav, fps/fes, SHC, Syk (carboxy-terminal SH2), 3BP2, and HCP (amino-terminal SH2 domain, also called PTP1C and SHPTP1). As predicted, SH2 domains from proteins that fall into group I on the basis of a Phe or Tyr at the beta D5 position (GRB-2, 3BP2, Csk, fps/fes, Syk C-terminal SH2) select phosphopeptides with the general motif phospho-Tyr-hydrophilic (residue)-hydrophilic (residue)-hydrophobic (residue). The SH2 domains of SHC and HCP (group III proteins with Ile, Leu, of Cys at the beta D5 position) selected the general motif phospho-Tyr-hydrophobic-Xxx-hydrophobic, also as predicted. Vav, which has a Thr at the beta D5 position, selected phospho-Tyr-Met-Glu-Pro as the optimal motif. Each SH2 domain selected a unique optimal motif distinct from motifs previously determined for other SH2 domains. These motifs are used to predict potential sites in signaling proteins for interaction with specific SH2 domain-containing proteins. The Syk SH2 domain is predicted to bind to Tyr-hydrophilic-hydrophilic-Leu/Ile motifs like those repeated at 10-residue intervals in T- and B-cell receptor-associated proteins. SHC is predicted to bind to a subgroup og these same motifs. A structural basis for the association of Csk with Src family members is also suggested from these studies.

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Dissertations / Theses on the topic "Src homology 2 domain (SH2 domain)"

1

Tan, Pauline H. "Sequence Specificity of Src Homology-2 Domains." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1324406526.

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Wavreille, Anne-Sophie Marie. "SRC homology 2 domain proteins binding specificity from combinatorial chemistry to cell-permeable inhibitors /." Columbus, Ohio : Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1164738844.

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Drapeau, Nicolas. "L’expression de SHP-1 induite par l’hyperglycémie inhibe les actions de l’insuline dans les podocytes." Mémoire, Université de Sherbrooke, 2014. http://savoirs.usherbrooke.ca/handle/11143/129.

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Résumé : Les podocytes, cellules épithéliales rénales, sont nécessaires au maintien de la structure et de la fonction de filtration des glomérules rénaux. La dédifférenciation et l’apoptose des podocytes sont des évènements précoces de la néphropathie diabétique. Des études ont rapporté que l’insuline est nécessaire à la survie des podocytes puisque la délétion du récepteur à l’insuline dans les podocytes de souris entraîne une pathologie glomérulaire semblable à la néphropathie. D’autres études ont montré que la protéine tyrosine phosphatase Src homology-2 domain-containing phosphatase-1 (SHP-1) inhibe les voies de signalisation de l’insuline au niveau du foie et du muscle en déphosphorylant la sous-unité bêta du récepteur à l’insuline (IRβ) et la kinase Phosphatidylinositide 3-kinase (PI3K). Il a récemment été démontré que l’expression de SHP-1 est élevée dans les cortex rénaux de souris diabétiques. Nous avons donc émis l’hypothèse que l’expression de SHP-1 induite par l’hyperglycémie altère les actions de l’insuline dans les podocytes. Nous avons premièrement utilisé un modèle in vivo de souris diabétiques de type 1 (Ins2+/C96Y; Akita). Comparées aux souris contrôles (Ins2+/+), les souris Akita présentaient une apoptose élevée des podocytes ainsi qu’une perte des pédicelles. La phosphorylation de la protéine kinase B (Akt) et de Extracellular signal-regulated kinase 1/2 (ERK1/2), suite à une injection systémique d’insuline, était également significativement diminuée dans les cortex rénaux des souris Akita. Cette diminution correspondant à une résistance à l’insuline corrélait avec une augmentation de deux fois de l’expression de SHP-1 dans les glomérules. Nous avons ensuite utilisé une lignée immortalisée de podocytes murins en culture et avons observé que l’exposition à des concentrations élevées de glucose (HG; 25 mM) pendant 96 h, entraînait l’augmentation de l’expression de marqueurs apoptotiques et de l’activité enzymatique de caspase-3/7 en comparaison aux concentrations normales de glucose (NG; 5,6 mM). L’exposition en HG a augmenté l’expression de l’ARNm et protéique de SHP-1, en plus de réduire la signalisation de l’insuline dans les podocytes. La surexpression de la forme dominante-négative de SHP-1 dans les podocytes a permis de renverser les effets de HG et de restaurer les actions de l’insuline. Finalement, l’augmentation de l’expression de SHP-1, tant in vivo qu’in vitro, a été directement corrélée à son association avec IRβ et à la diminution de la phosphorylation de IRβ, Akt et ERK1/2 suite à une stimulation à l’insuline. En conclusion, nous avons montré que l’expression élevée de SHP-1 dans les glomérules cause une résistance à l’insuline et la mort des podocytes contribuant ainsi à la néphropathie diabétique. // Abstract : Podocytes are epithelial renal cells required to preserve glomerular structure and filtration. Their dedifferentiation and apoptosis are early events of diabetic nephropathy progression. Previous studies have shown that insulin action is critical for podocyte survival since deletion of its receptor lead to a glomerular pathology similar to nephropathy. It has also been demonstrated that Src homology-2 domain-containing phosphatase-1 (SHP-1), a protein tyrosine phosphatase, inhibits insulin signaling pathway in liver and muscle by dephosphorylating tyrosine residues on insulin receptor beta-subunit (IRβ) and the Phosphatidylinositide 3-kinase (PI3K). A recent study concluded that SHP-1 is elevated in kidney cortex of type 1 diabetic mice. We hypothesized that hyperglycemia-induced SHP-1 expression may affect insulin actions in podocytes. To confirm this hypothesis, we used type 1 diabetic Akita mice (Ins2+/C96Y). Compared to control littermate mice (Ins2+/+), Akita mice developed elevated podocyte foot process effacement and podocyte apoptosis. In contrast to control mice, insulin-stimulated protein kinase B (Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was remarkably reduced in renal podocytes of Akita mice. This phosphorylation diminution associated to a renal insulin resistance was correlated with a two-fold increase of SHP-1 expression in the glomeruli. We then used cultured murine podocytes cell line to confirm our in vivo results. Podocytes exposed to high glucose concentration (HG; 25 mM) for 96 h exhibited high levels of apoptotic markers and caspase-3/7 enzymatic activity as compared to normal glucose concentration (NG; 5,6 mM). HG exposure raised mRNA and protein levels of SHP-1 and reduced the insulin-signaling pathway in podocytes. Overexpression of dominant-negative SHP-1 in podocytes prevented HG effects and restored insulin actions. Finally, elevated SHP-1 expression induced by high glucose levels was directly correlated to an increased association with insulin receptor-β subunit (IRβ) in vitro and in vivo. This association is therefore leading to the reduction of both IRβ phosphorylation and insulin-stimulated Akt and ERK phosphorylation. In conclusion, our results showed that high levels of SHP-1 in glomeruli cause insulin resistance and podocyte loss, thereby contributing to diabetic nephropathy.

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Desponts, Caroline. "The role of Src homology 2 domain containing 5' inositol phosphatase 1 (SHIP) in hematopoietic cells." [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001591.

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Mannell, Hanna. "The role of Src-homology 2 domain containing tyrosine phosphatase 2 in growth factor dependent endothelial signalling and angiogenesis." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-70966.

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Okazaki, Taku. "PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine." Kyoto University, 2003. http://hdl.handle.net/2433/148707.

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Nordqvist, Sarah. "Biological Markers of Fertility." Doctoral thesis, Uppsala universitet, Obstetrik & gynekologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-234067.

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Infertility affects 15 % of couples, which corresponds to 60 - 80 million worldwide. The microenvironments in which the oocyte, embryo and fetus mature are vital to the establishment and development of a healthy pregnancy. Different biological systems, such as angiogenesis, the immune system and apoptosis need to be adequately regulated for pregnancy to occur and progress normally. The overall aim of this thesis was to investigate the impact of Histidine-rich glycoprotein (HRG) and Src homology 2 domain-containing adapter protein B (SHB) on human female fertility. HRG is a plasma protein that regulates angiogenesis, the immune system, coagulation/fibrinolysis and apoptosis, by building complexes with various ligands. The impact of HRG on fertility is studied here for the first time. HRG is present in follicular fluid, the Fallopian tube, endometrium, myometrium and placenta. HRG distribution within embryo nuclei depends on developmental stage. Blastocysts express and secrete HRG. The HRG C633T single nucleotide polymorphism (SNP) appears to affect the chance of pregnancy and, correspondingly, parameters associated with pregnancy in IVF. Additionally, this HRG genotype may increase the risk in IVF of only developing embryos unfit for transfer. SHB is an adaptor protein involved in intracellular signaling complexes that regulate angiogenesis, the immune system and cell proliferation/apoptosis. Shb knockout mice have altered oocyte/follicle maturation and impaired embryogenesis. The impact of three SHB polymorphisms (rs2025439, rs13298451 and rs7873102) on human fertility is studied for the first time. The SNP prevalences did not differ between infertile and fertile women. BMI, gonadotropin dosages, the percentage of immature oocytes, the number of fertilized oocytes, the percentage of good-quality embryos and the day of embryo transfer seems to be affected by SHB genotype. In conclusion, HRG and SHB appear to influence female fertility. They are potential biomarkers that might be used for predicting pregnancy chance in infertile women. Knowledge of these genotypes may improve patient counseling and individualization of treatment.

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Chen, Grace Yi-Ying. "Functional Analysis of Adapter Protein c-Abl Src Homology 3 Domain-binding Protein 2." Thesis, 2009. http://hdl.handle.net/1807/17740.

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3BP2 is a pleckstrin homology (PH) domain- and Src homology 2 (SH2) domain-containing adapter protein that has been linked through genetic evidence to a rare human disease called cherubism 146. 3BP2 was originally cloned in a screen to identify c-Abl SH3 binding proteins 23,24. In overexpression studies, 3BP2 has been implicated as a positive regulatory adapter molecule coupled to immunoreceptor on T cells 67,69,70, B cells 68, NK cells 71-73 and mast cells 74,75. It was also evident that 3BP2 forms complexes with a number of signaling molecules, such as Zap-70, LAT, phospholipase C-γ1 (PLC-γ1), Grb2, Cbl, and Fyn in Jurkat cells 67 and Vav1, Vav2, PLC-γ, and Syk in Daudi B cells 68. Despite the growing body of biochemical data to support the importance of 3BP2 in cells of the hematopoietic lineage, a clear picture of the biological function of 3BP2 has yet to emerge. To elucidate the in vivo function of 3BP2, our laboratory has generated 3BP2 gene-deficient mice through homologous recombination 452. The 3BP2-deficient (3BP2-/-) mice were born at the expected Mendelian frequency and were fertile and viable. 3BP2-/- mice accumulate splenic marginal-zone (MZ) B cells, possess a reduced frequency of peritoneal B-1 B cells, and have a diminished thymus-independent type 2 (TI-2) antigen response. 3BP2-/- B cells demonstrate diminished proliferation and cell survival following cross-linking of the B-cell receptor (BCR). Following BCR ligation, 3BP2 might be recruited to BCR complex through its inducible interaction with BCR costimulatory molecule CD19. In the absence of 3BP2, the activation of BCR downstream effectors such as MAPK Erk1/2, JNK, and c-Abl is normal; however, 3BP2 deficiency leads to defects in Syk phosphorylation and calcium flux. In addition to defects in peripheral B cell activities, 3BP2 deficiency contributes to defects in neutrophil activities. In response to the chemotactic peptide, fMLF, 3BP2-/- neutrophils fail to establish directional migration in vitro. There is a defect in the accumulation of filamentous actin at the leading edge of migrating 3BP2-/- neutrophils which might be responsible for the random movement of these cells under shallow gradient of fMLF. In vivo, there is a delay in the recruitment of circulating neutrophils to the site of chemically induced inflammation in 3BP2-/- mice. Compared to wildtype neutrophils, 3BP2-/- neutrophils fail to properly produce superoxide anion (O2-) following fMLF stimulation. Defects in both directional migration and superoxide production of 3BP2-/- neutrophils might contribute to the reduction in bacteria clearance and the increased mortality in 3BP2-/- mice post Listeria Monocytogenes infection. In Chapter 1 of this thesis, I have reviewed basic structures and functions of the domain modules found in adapter proteins. In addition, I have reviewed the findings from numerous reports on the function of 3BP2 in different cell types. A discussion of the physical appearance and some of the initial characterization of 3BP2-deficient mice (3BP2-/-) we have generated in our laboratory are included in Chapter 1. The second part of Chapter 1 consists of an introduction on B cell receptor signaling pathway and B-cell development and activation. A discussion of G protein-coupled receptor-mediated neutrophil functions can also be found in Chapter 1. Chapter 2 contains all the methods and materials used in my study. Chapter 3 includes the characterization of peripheral B cell compartment of 3BP2-/- mice as well as the role of 3BP2 downstream of B-cell antigen receptor and in T-independent immune response. In chapter 4, I present data from experiments designed to examine the role of 3BP2 downstream of a G protein-coupled receptor, fMLF receptor, of neutrophils. I also show the requirement of 3BP2 in the clearance of Listeria Monocytogenes. In chapter 5, I propose two models for 3BP2 action based on the findings in B cells and neutrophils and discuss future areas for investigation.

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Yu-ChihWang and 王郁芷. "Suppression of IFN-γ Signaling by Src Homology-2 Domain-containing Phosphatase 2 During Helicobacter pylori Infection." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/6puydv.

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碩士
國立成功大學
臨床醫學研究所
101
Helicobacter pylori (H. pylori), a gram-negative spiral bacteria, infection not only induce gastric inflammation but also increase the risk of gastric tumorigenesis. Interferon (IFN)-γ has antimicrobial effects; however, H. pylori infection elevates IFN-γ-mediated gastric inflammation and may suppress IFN-γ signaling as a strategy to avoid immune destruction through an as-yet unknown mechanism. This study was aimed at investigating the mechanism of H. pylori-induced IFN-γ resistance. Pre-treatment of IFN-γ decreased cytotoxin-associated gene A (CagA) expression following H. pylori infection. Post-infection viable, but not heat-killed, clinical isolates of wild-type H. pylori strain HP238 decreased IFN-γ-induced phosphorylation of signal transducers and activators of transcription 1 and promoter transactivation of IFN-regulatory factor 1. HP238 infection caused an increase in the C-terminal tyrosine phosphorylation of Src homology-2 domain-containing phosphatase (SHP) 2 and its downstream signaling of MEK/ERK. Inhibiting SHP2 by using specific inhibitors and shRNA interference reversed HP238-induced IFN-γ resistance. The CagA isogenic mutant strain HP238CagAm failed to induce IFN-γ resistance and morphological change known as hummingbird phenomenon, indicating that CagA regulates these effects. Notably, HP238 and HP238CagAm both caused SHP2 phosphorylation; furthermore, imaging and biochemical analyses demonstrated CagA-mediated membrane-associated binding with phosphorylated SHP2. Without CagA, HP238CagAm infection only did not cause IFN-γ resistance even SHP2 is phosphorylated. CagA-independent generation of reactive oxygen species (ROS) contributed to H. pylori-induced SHP2 phosphorylation and IFN-γ resistance when CagA was concurrently present. This finding not only provides an alternative mechanism for how CagA and ROS co-regulate SHP2 activation but may also explain their roles in H. pylori-induced IFN-γ suppression of IFN-γ signaling.

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Mannell, Hanna Karin [Verfasser]. "The role of Src-homology 2 domain containing tyrosine phosphatase 2 in growth factor dependent endothelial signalling and angiogenesis / Hanna Karin Mannell." 2007. http://d-nb.info/985207248/34.

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Book chapters on the topic "Src homology 2 domain (SH2 domain)"

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Dempsey, Brian R., Anne C. Rintala-Dempsey, Gary S. Shaw, Yuan Xiao Zhu, A. Keith Stewart, Jaime O. Claudio, Constance E. Runyan, et al. "Src Homology Region 2 (SH2)-Domain Phosphatase or Src Homology Region 2 Domain-Containing PTP-1 (SHP-1 or SH-PTP1)." In Encyclopedia of Signaling Molecules, 1779. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_101271.

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Dempsey, Brian R., Anne C. Rintala-Dempsey, Gary S. Shaw, Yuan Xiao Zhu, A. Keith Stewart, Jaime O. Claudio, Constance E. Runyan, et al. "Src Homology 2 (SH2) Domain–Containing Leukocyte Protein of 76 kDa." In Encyclopedia of Signaling Molecules, 1779. New York, NY: Springer New York, 2012. http://dx.doi.org/10.1007/978-1-4419-0461-4_101270.

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Overduin, Michael, Carlos B. Rios, Bruce J. Mayer, David Baltimore, and David Cowburn. "Methods used in the Assignments of the 1H and 15N resonances of the c-Abl src homology 2 (SH2) domain." In NMR of Biological Macromolecules, 189–98. Berlin, Heidelberg: Springer Berlin Heidelberg, 1994. http://dx.doi.org/10.1007/978-3-642-79158-1_9.

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Sturla, Lisa-Marie, Pascal Zinn, and Ekkehard Kasper. "Suppression of Cellular Senescence in Glioblastoma: Role of Src Homology Domain-Containing Phosphatase 2." In Tumor Dormancy, Quiescence, and Senescence, Volume 1, 249–59. Dordrecht: Springer Netherlands, 2013. http://dx.doi.org/10.1007/978-94-007-5958-9_21.

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"Src Homology 2 (SH2) Domain." In Encyclopedia of Immunotoxicology, 831. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-642-54596-2_201376.

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"Src Homology Region 2 [SH2]-Domain Phosphatase or Src Homology Region 2 Domain-Containing PTP-1." In Encyclopedia of Signaling Molecules, 5145. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_103639.

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"Src Homology 2 (SH2) Domain–Containing Leukocyte Protein of 76 kDa." In Encyclopedia of Signaling Molecules, 5145. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_103637.

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"SH 2 (src homology domain)." In Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 1801. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_15516.

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"Src Homology 2 Domain-Containing Transforming Protein C1." In Encyclopedia of Signaling Molecules, 5145. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_103638.

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Conference papers on the topic "Src homology 2 domain (SH2 domain)"

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Lin, Ping-Yi, Yao-Li Chen, Pei-Yi Chu, and Kuen-Feng Chen. "Abstract 1799: Src homology region 2 domain-containing phosphatase-1 (SHP-1) is overexpressed in hepatocellular carcinoma." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-1799.

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Tai, Wei-Tien, Chung-Wai Shiau, Pei-Jer Chen, Ann-Lii Cheng, and Kuen-Feng Chen. "Abstract 2175: Src homology region 2 domain-containing phosphatase-1 is a major target of sorafenib in hepatocellular carcinoma." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-2175.

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Chang, Y.-F., Y. Wang, and GL Greene. "Abstract P6-11-14: Src homology 2 domain containing transforming protein 1 and steroid receptor coactivator-3 as novel targets for triple-negative breast cancer." In Abstracts: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, Texas. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.sabcs16-p6-11-14.

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Reports on the topic "Src homology 2 domain (SH2 domain)"

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Mayer, Bruce J. Probing the Tyrosine Phosphorylation State in Breast Cancer by Src Homology 2 Domain Binding. Fort Belvoir, VA: Defense Technical Information Center, August 2004. http://dx.doi.org/10.21236/ada428932.

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2

Mayer, Bruce J. Probing the Tyrosine Phosphorylation State in Breast Cancer by Src Homology 2 Domain Binding. Fort Belvoir, VA: Defense Technical Information Center, August 2006. http://dx.doi.org/10.21236/ada463307.

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