Journal articles: 'Tyrosine protein phosphatase non-receptor type 11'

1

Becker, Helen M., Barbara Schnell, Joba M. Arikkat, Markus Schuppler, Martin J. Loessner, Michael Fried, Gerhard Rogler, and Michael Scharl. "Protein Tyrosine Phosphatase Non-Receptor Type 2 Regulates NLRP3 Inflammasome Activation." Gastroenterology 140, no. 5 (May 2011): S—633. http://dx.doi.org/10.1016/s0016-5085(11)62618-8.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

Scharl, Michael, Kacper A. Wojtal, Helen M. Becker, Anne Fischbeck, Joba M. Arikkat, Theresa Pesch, Silvia Kellermeier, et al. "Protein Tyrosine Phosphatase Non-Receptor Type 2 is a Regulator of Authophagosome Function." Gastroenterology 140, no. 5 (May 2011): S—172. http://dx.doi.org/10.1016/s0016-5085(11)60696-3.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Sahu, Mahadev, Armiya Sultan, and Manas Ranjan Barik. "Molecular docking and high throughput screening of designed potent inhibitor to PTPN11 involved in Peptic Ulcer." South Asian Journal of Experimental Biology 6, no. 4 (December 23, 2016): 124–30. http://dx.doi.org/10.38150/sajeb.6(4).p124-130.

Full text

Abstract:

In the current study we carried out computational drug designing and dock-ing studies on Tyrosine-protein phosphatase non-receptor type 11 (PTPN11). Scaffold selection was based on the functional properties of PTPN11. Leads were identified based on several physiochemical properties and we created our library with those new molecules that were generated based on Lipinski's rule of five. Further, we carried out high throughput screening on 21 molecules from scaffolds selected. Screening of molecules was based on the criterions such as, TOPKAT (toxicity analysis) and ADMET (absorption, distribution, metabolism, elimination) properties. Among the ligands de-signed, only one compound was identified to have premium interaction within the targeted domain. Pharmacophore was generated and analyzed for selected drug candidate. Our results suggest that O-(3-hydroxy-4-methoxyphenyl) S-methyl dithio dicarbonate is a potent drug molecule in terms of physiochemical and docking properties. In conclusion, the identified compound has great potential to inhibit tyrosine-protein phosphatase non-receptor type 11 (PTPN11).

APA, Harvard, Vancouver, ISO, and other styles

4

Kang, J., P. Posner, and C. Sumners. "Angiotensin II type 2 receptor stimulation of neuronal K+ currents involves an inhibitory GTP binding protein." American Journal of Physiology-Cell Physiology 267, no. 5 (November 1, 1994): C1389—C1397. http://dx.doi.org/10.1152/ajpcell.1994.267.5.c1389.

Full text

Abstract:

Angiotensin II (ANG II) elicits an ANG II type 2 (AT2) receptor-mediated increase in outward K+ current (IK; delayed rectifier K+ current) in neurons cocultured from rat hypothalamus and brain stem. Here we have shown that the AT2-receptor-mediated stimulation of neuronal IK by ANG II (100 nM) was abolished by pretreatment of cultures with pertussis toxin (PTX; 200 ng/ml) and by intracellular application of an antibody against the inhibitory guanine nucleotide (GTP) binding protein (anti-Gi alpha, 1:200). Antibodies against other GTP binding proteins (anti-Go alpha, 1:50 and 1:200; anti-Gq/11 alpha, 1:200) did not alter the AT2-receptor-mediated stimulation of neuronal IK by ANG II (100 nM). Furthermore, this effect of ANG II (100 nM) was inhibited by the serine/threonine phosphatase inhibitor okadaic acid (1-10 nM) and by anti-type 2A protein phosphatase (PP2A) antibodies but not by the tyrosine phosphatase inhibitor sodium orthovanadate (1 mM). Thus we have identified key components (Gi and PP2A) of the signal transduction pathway that is responsible for the AT2-receptor-mediated stimulation of neuronal K+ currents.

APA, Harvard, Vancouver, ISO, and other styles

5

HEINRICH, Peter C., Iris BEHRMANN, Gerhard MÜLLER-NEWEN, Fred SCHAPER, and Lutz GRAEVE. "Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway1." Biochemical Journal 334, no. 2 (September 1, 1998): 297–314. http://dx.doi.org/10.1042/bj3340297.

Full text

Abstract:

The family of cytokines signalling through the common receptor subunit gp130 comprises interleukin (IL)-6, IL-11, leukaemia inhibitory factor, oncostatin M, ciliary neurotrophic factor and cardiotrophin-1. These so-called IL-6-type cytokines play an important role in the regulation of complex cellular processes such as gene activation, proliferation and differentiation. The current knowledge on the signal-transduction mechanisms of these cytokines from the plasma membrane to the nucleus is reviewed. In particular, we focus on the assembly of receptor complexes after ligand binding, the activation of receptor-associated kinases of the Janus family, and the recruitment and phosphorylation of transcription factors of the STAT family, which dimerize, translocate to the nucleus, and bind to enhancer elements of respective target genes leading to transcriptional activation. The important players in the signalling pathway, namely the cytokines and the receptor components, the Janus kinases Jak1, Jak2 and Tyk2, the signal transducers and activators of transcription STAT1 and STAT3 and the tyrosine phosphatase SHP2 [SH2 (Src homology 2) domain-containing tyrosine phosphatase] are introduced and their structural/functional properties are discussed. Furthermore, we review various mechanisms involved in the termination of the IL-6-type cytokine signalling, namely the action of tyrosine phosphatases, proteasome, Jak kinase inhibitors SOCS (suppressor of cytokine signalling), protein inhibitors of activated STATs (PIAS), and internalization of the cytokine receptors via gp130. Although all IL-6-type cytokines signal through the gp130/Jak/STAT pathway, the comparison of their physiological properties shows that they elicit not only similar, but also distinct, biological responses. This is reflected in the different phenotypes of IL-6-type-cytokine knock-out animals.

APA, Harvard, Vancouver, ISO, and other styles

6

Idrees, Muhammad, Lianguang Xu, Seok-Hwan Song, Myeong-Don Joo, Kyeong-Lim Lee, Tahir Muhammad, Marwa El Sheikh, Tabinda Sidrat, and Il-Keun Kong. "PTPN11 (SHP2) Is Indispensable for Growth Factors and Cytokine Signal Transduction During Bovine Oocyte Maturation and Blastocyst Development." Cells 8, no. 10 (October 18, 2019): 1272. http://dx.doi.org/10.3390/cells8101272.

Full text

Abstract:

This study was aimed to investigate the role of SHP2 (Src-homology-2-containing phosphotyrosine phosphatase) in intricate signaling networks invoked by bovine oocyte to achieve maturation and blastocyst development. PTPN11 (Protein Tyrosine Phosphatase, non-receptor type 11) encoding protein SHP2, a positive transducer of RTKs (Receptor Tyrosine Kinases) and cytokine receptors, can play a significant role in bovine oocyte maturation and embryo development, but this phenomenon has not yet been explored. Here, we used different growth factors, cytokines, selective activator, and a specific inhibitor of SHP2 to ascertain its role in bovine oocyte developmental stages in vitro. We found that SHP2 became activated by growth factors and cytokines treatment and was highly involved in the activation of oocyte maturation and embryo development pathways. Activation of SHP2 triggered MAPK (mitogen-activated protein kinases) and PI3K/AKT (Phosphoinositide 3-kinase/Protein kinase B) signaling cascades, which is not only important for GVBD (germinal vesical breakdown) induction but also for maternal mRNA translation. Inhibition of phosphatase activity of SHP2 with PHPS1 (Phenylhydrazonopyrazolone sulfonate 1) reduced oocytes maturation as well as bovine blastocyst ICM (inner cell mass) volume. Supplementation of LIF (Leukemia Inhibitory Factor) to embryos showed an unconventional direct relation between p-SHP2 and p-STAT3 (Signal transducer and activator of transcription 3) for blastocyst ICM development. Other than growth factors and cytokines, cisplatin was used to activate SHP2. Cisplatin activated SHP2 modulate growth factors effect and combine treatment significantly enhanced quality and rate of developed blastocysts.

APA, Harvard, Vancouver, ISO, and other styles

7

Honda, H., J. Inazawa, J. Nishida, Y. Yazaki, and H. Hirai. "Molecular cloning, characterization, and chromosomal localization of a novel protein-tyrosine phosphatase, HPTP eta." Blood 84, no. 12 (December 15, 1994): 4186–94. http://dx.doi.org/10.1182/blood.v84.12.4186.bloodjournal84124186.

Full text

Abstract:

Protein-tyrosine phosphatases (PTPases) are considered to play an important role in signal transduction. We previously identified partial sequences of three novel PTPases in a human leukemic cell line. F-36P. We describe here cloning, characterization, and chromosomal localization of one of the newly identified PTPases, termed as HPTP eta (human protein-tyrosine phosphatase eta). The deduced amino acid sequence was composed of an extracellular region homologous to fibronectin type III repeats, a transmembrane region, and a cytoplasmic region containing a single PTPase-like domain. Based on its primary structure, this clone belongs to type-III receptor-type PTPases. The PTPase-like domain showed PTPase activity when expressed in Escherichia coli. Antibody against the extracellular region detected a protein of 220 to 250 kD in human hematopoietic cell lines expressing HPTP eta mRNA. The antibody also recognized a protein of approximately the same molecular weight in COS cells transfected with HPTP eta cDNA, indicating that the antibody specifically recognized HPTP eta gene product and that the cloned cDNA contained full-length coding region. The chromosomal localization determined by fluorescence in situ hybridization showed that the HPTP eta gene was located at chromosome 11p11.2 on the short arm of chromosome 11, which is frequently lost or deleted in human carcinomas.

APA, Harvard, Vancouver, ISO, and other styles

8

Scharl, Michael, Kacper A. Wojtal, Helen M. Becker, Anne Fischbeck, Joba M. Arikkat, Theresa Pesch, Silvia Kellermeier, et al. "The Crohn's Disease Associated Variant of the Protein Tyrosine Phosphatase Non-Receptor Type 2 Gene Affects Cellular Responses to Invading Listeria Monocytogenes." Gastroenterology 140, no. 5 (May 2011): S—496. http://dx.doi.org/10.1016/s0016-5085(11)62052-0.

Full text

APA, Harvard, Vancouver, ISO, and other styles

9

G, Bhusnure Omprakash. "In-silico exploration of piperine for invent proton pump and protein phosphatase non-receptor Inhibitors in gastric and peptic ulcer." Journal of medical pharmaceutical and allied sciences 11, no. 6 (December 31, 2022): 5334–38. http://dx.doi.org/10.55522/jmpas.v11i6.1865.

Full text

Abstract:

Anti-ulcer medicines that inhibit the H/K-ATPase enzyme by covalently binding to a cysteine residue of proton pump inhibitors. Through the aforementioned processes, tyrosine-protein phosphatase non-receptor type 11 (PTPN11) causes aberrant mitogenic signals and elongated morphological alterations, as well as the growth and progression of peptic ulcer and gastric cancer.Piperine is an antioxidant derived from the Piper Longum herb. Molecular docking studies and virtual screening were used to investigate it as an H/K ATPase and PTPN11 inhibitor. The Molecular Docking examination was conducted using the Pyrx 0.8 version free database, while virtual screening was conducted using Biovia Discovery Studio software.H/K-ATPase and PTPN11 have substantial binding affinity of 7.5 and 8.6 kcal/mol, respectively, according to molecular docking investigations. Piperine's anti-ulcer efficacy appears to be aided by H/K-ATPase and PTPN11 binding

APA, Harvard, Vancouver, ISO, and other styles

10

Scharl, Michael, Kacper A. Wojtal, Anne Fischbeck, Joba M. Arikkat, Theresa Pesch, Silvia Kellermeier, Stephan R. Vavricka, Michael Fried, Declan F. McCole, and Gerhard Rogler. "The Crohn's Disease Candidate Gene, Protein Tyrosine Phosphatase Non-Receptor Type 2, Regulates Muramyldipetide-Induced NOD2-Dependent Effects in Human Monocytes and Fibroblasts." Gastroenterology 140, no. 5 (May 2011): S—487. http://dx.doi.org/10.1016/s0016-5085(11)62007-6.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Wimmer-Kleikamp, Sabine H., Eva Nievergall, Kristina Gegenbauer, Samantha Adikari, Mariam Mansour, Trina Yeadon, Andrew W. Boyd, Neill R. Patani, and Martin Lackmann. "Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells." Blood 112, no. 3 (August 1, 2008): 721–32. http://dx.doi.org/10.1182/blood-2007-11-121681.

Full text

Abstract:

Abstract Signaling by Eph receptors and cell-surface ephrin ligands modulates adhesive cell properties and thereby coordinates cell movement and positioning in normal and oncogenic development. While cell contact–dependent Eph activation frequently leads to cell-cell repulsion, also the diametrically opposite response, cell-cell adhesion, is a probable outcome. However, the molecular principles regulating such disparate functions have remained controversial. We have examined cell-biologic mechanisms underlying this switch by analyzing ephrin-A5–induced cell-morphologic changes of EphA3-positive LK63 pre-B acute lymphoblastic leukemia cells. Their exposure to ephrin-A5 surfaces leads to a rapid conversion from a suspended/nonpolarized to an adherent/polarized cell type, a transition that relies on EphA3 functions operating in the absence of Eph-kinase signaling. Cell morphology change and adhesion of LK63 cells are effectively attenuated by endogenous protein tyrosine phosphatase (PTP) activity, whereby PTP inhibition and productive EphA3-phosphotyrosine signaling reverse the phenotype to nonadherent cells with a condensed cytoskeleton. Our findings suggest that Eph-associated PTP activities not only control receptor phosphorylation levels, but as a result switch the response to ephrin contact from repulsion to adhesion, which may play a role in the pathology of hematopoietic tumors.

APA, Harvard, Vancouver, ISO, and other styles

12

Noordam, C., P. G. M. Peer, I. Francois, J. De Schepper, I. van den Burgt, and B. J. Otten. "Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, non-receptor-type 11." European Journal of Endocrinology 159, no. 3 (September 2008): 203–8. http://dx.doi.org/10.1530/eje-08-0413.

Full text

Abstract:

ContextNoonan syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. Short-term effect of GH therapy in NS is beneficial, reports on the effect on adult height are scarce.ObjectiveTo determine the effect of long-term GH therapy in children with NS.DesignTwenty-nine children with NS were treated with GH until final height was reached.SettingHospital endocrinology departments.PatientsChildren with the clinical diagnosis of NS, with mean age at the start of therapy of 11.0 years, 22 out of 27 tested children had a mutation in the protein tyrosine phosphatase, non-receptor-type 11 gene (PTPN11 gene).InterventionsGH was administered subcutaneously at 0.05 mg/kg per day until growth velocity was 1 cm/6 months.Main outcome measureLinear growth (height) was measured at 3-month intervals in the first year and at 6-month intervals thereafter until final height.ResultsAt the start of treatment, median height SDS (H-SDS) was −2.8 (−4.1 to −1.8) and 0.0 (−1.4 to +1.2), based on national and Noonan standards respectively. GH therapy lasted for 3.0–10.3 years (median, 6.4), producing mean gains in H-SDS of +1.3 (+0.2 to +2.7) and +1.3 (−0.6 to +2.4), based on national and Noonan standards respectively. In 22 children with a mutation in PTPN11 mean gain in H-SDS for National standards was +1.3, not different from the mean gain in the five children without a mutation in PTPN11+1.3 (P=0.98).ConclusionLong-term GH treatment in NS leads to attainment of adult height within the normal range in most patients.

APA, Harvard, Vancouver, ISO, and other styles

13

Oak, Shilpa, Cang Tran, Maria-Olivia Castillo, Shanthie Thamotharan, Manikkavasagar Thamotharan, and Sherin U. Devaskar. "Peroxisome proliferator-activated receptor-γ agonist improves skeletal muscle insulin signaling in the pregestational intrauterine growth-restricted rat offspring." American Journal of Physiology-Endocrinology and Metabolism 297, no. 2 (August 2009): E514—E524. http://dx.doi.org/10.1152/ajpendo.00008.2009.

Full text

Abstract:

The effect of early intervention with a peroxisome proliferator-activated receptor-γ (PPARγ) agonist on skeletal muscle GLUT4 translocation and insulin signaling was examined in intrauterine (IUGR) and postnatal (PNGR) growth-restricted pregestational female rat offspring. Rosiglitazone [11 μmol/day provided from postnatal day (PN)21 to PN60] improved skeletal muscle insulin sensitivity and GLUT4 translocation in prenatal nutrient restriction [50% calories from embryonic day (e)11 to e21; IUGR] with (IUGR+PNGR) and without (IUGR) postnatal nutrient restriction (50% calories from PN1 to PN21; PNGR) similar to that of control (ad libitum feeds throughout; Con) ( n = 6 each). This was accomplished by diminished basal and improved insulin-responsive GLUT4 association with the plasma membrane in IUGR, IUGR+PNGR, and PNGR mimicking that in Con ( P < 0.005). While no change in p85-phosphatidylinositol 3-kinase (PI3-K) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was observed, a decrease in protein tyrosine phosphatase 1B (PTP1B; P < 0.0002) and SH2-containing protein tyrosine phosphatase 2 (SHP2; P < 0.05) contributing to the rosiglitazone-induced insulin sensitivity was seen only in IUGR+PNGR. In contrast, an increase in phosphorylated 5′-adenosine monophosphate kinase (pAMPK; P < 0.04) and insulin responsiveness of phosphorylated phosphoinositide-dependent protein kinase-1 (pPDK1; P < 0.05), pAkt ( P < 0.01), and particularly pPKCζ ( P < 0.0001) and its corresponding enzyme activity ( P < 0.005) were observed in all four experimental groups. We conclude that early introduction of PPARγ agonist improved skeletal muscle activation of AMPK and insulin signaling, resulting in insulin-independent AMPK and insulin-responsive GLUT4 association with plasma membranes in IUGR, IUGR+PNGR, and PNGR adult offspring, similar to that of Con. These findings support a role for insulin sensitizers in preventing the subsequent development of gestational or type 2 diabetes mellitus in intrauterine and postnatal growth-restricted offspring.

APA, Harvard, Vancouver, ISO, and other styles

14

Motiwala, Tasneem, Satavisha Roy, Shujun Liu, Sebastian Schwind, Rainer Claus, Xiaokui Mo, Ramiro Garzon, et al. "Aberrant Epigenetic Suppression of the Ptprot Gene Encoding a Protein Tyrosine Phosphatase Targeting KIT in Acute Myeloid Leukemia." Blood 120, no. 21 (November 16, 2012): 1322. http://dx.doi.org/10.1182/blood.v120.21.1322.1322.

Full text

Abstract:

Abstract Abstract 1322 Recent studies have suggested that deregulated expression of tyrosine phosphatases and the resulting alteration in the phosphorylation status of their substrates play a significant role in the oncogenic function of tyrosine-phosphorylated proteins. Over the past decade we have been studying the tumor suppressive function of protein tyrosine phosphatase receptor-type O (PTPRO). The gene for PTPRO encodes two functional isoforms, full-length form (PTPRO-FL) and a truncated form (PTPROt) that are expressed in a tissue-specific manner. PTPROt is primarily expressed in hematopoietic cells. It is, however, transcriptionally and epigenetically suppressed in CLL-like cell lines and primary CLL [Clin Cancer Res. 2007 Jun 1;13(11):3174–81, Blood. 2011 Dec 1;118(23):6132–40]. We have now shown that PTPROt is also hypermethylated in a discovery set of primary AML samples (n=77) provided by the University hospital Ulm biobank relative to bone marrow from normal controls. Analysis of the AML cell lines Kasumi-1 and ME-1 cells also showed dramatically reduced PTPROt expression relative to THP-1 and MV4-11 cells. Treatment of Kasumi-1 cells with the hypomethylating agent decitabine led to re-activation of PTPROt at both RNA and protein levels. PTPRO CpG island (CGI), methylated in Kasumi-1 cells, became hypomethylated following treatment with decitabine. Similarly, bone marrow samples from elderly AML patients who received decitabine 20 mg/m2/day – 10 days on the OSU 07017 study exhibited hypomethylation and upregulation of PTPROt. To further evaluate the functional significance of hypermethylation and silencing of PTPROt in AML, we then searched for potential kinase substrates of the protein. Kasumi-1 and ME-1 cells (where PTPROt is suppressed) are both CBF cell lines characterized by RUNX1/RUNX1T1 [(8;21) translocation] and CBFB/MYH11 [inv(16)], respectively. While CBF AML patients are generally classified within a more favorable cytogenetic group, those cases harboring mutation in the KIT gene that results in constitutively active receptor tyrosine kinase have a poor outcome. In addition, increased expression of the encoded kinase protein occurs in ∼80% of CBF AML, regardless of KIT mutational status. Kasumi-1 and ME-1 cells are also characterized by mutated (constitutively active) and over-expressed KIT, respectively. Since tyrosine phosphorylation regulates the enzymatic activity and oncogenic function of KIT protein we hypothesized that this kinase could be a substrate of PTPROt and that expression of PTPROt would be critical to maintain control of its activity. Indeed, using in vitro substrate-trapping assay we demonstrated that KIT is a direct substrate of PTPROt. Further, in vivo studies conducted by co-transfecting KITD816V and PTPROt (wild type or catalytic site mutant) in H293T cells showed that phosphorylation of KIT at Y719, a read-out for KIT activity, was reduced when KIT was co-expressed with PTPROt-WT but not with vector control or catalytic site mutant of PTPROt. These observations suggest that suppression of PTPROt in CBF AML with over-expressed or mutated KIT could contribute to the leukemogeneic function of KIT. Given that the epigenetic suppression of PTPROt can be reversed by hypomethylating agent decitabine, it is possible that combination of decitabine and tyrosine kinase inhibitors with or without chemotherapy may represent a novel therapeutic approach in CBF AML. [Supported by grant CA101956] Disclosures: No relevant conflicts of interest to declare.

APA, Harvard, Vancouver, ISO, and other styles

15

Furlan, Veronika, Janez Konc, and Urban Bren. "Inverse Molecular Docking as a Novel Approach to Study Anticarcinogenic and Anti-Neuroinflammatory Effects of Curcumin." Molecules 23, no. 12 (December 18, 2018): 3351. http://dx.doi.org/10.3390/molecules23123351.

Full text

Abstract:

Research efforts are placing an ever increasing emphasis on identifying signal transduction pathways related to the chemopreventive activity of curcumin. Its anticarcinogenic effects are presumably mediated by the regulation of signaling cascades, including nuclear factor κB (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinases (MAPK). By modulating signal transduction pathways, curcumin induces apoptosis in malignant cells, thus inhibiting cancer development and progression. Due to the lack of mechanistic insight in the scientific literature, we developed a novel inverse molecular docking protocol based on the CANDOCK algorithm. For the first time, we performed inverse molecular docking of curcumin into a collection of 13,553 available human protein structures from the Protein Data Bank resulting in prioritized target proteins of curcumin. Our predictions were in agreement with the scientific literature and confirmed that curcumin binds to folate receptor β, DNA (cytosine-5)-methyltransferase 3A, metalloproteinase-2, mitogen-activated protein kinase 9, epidermal growth factor receptor and apoptosis-inducing factor 1. We also identified new potential protein targets of curcumin, namely deoxycytidine kinase, NAD-dependent protein deacetylase sirtuin-1 and -2, ecto-5′-nucleotidase, core histone macro-H2A.1, tyrosine-protein phosphatase non-receptor type 11, macrophage colony-stimulating factor 1 receptor, GTPase HRas, aflatoxin B1 aldehyde reductase member 3, aldo-keto reductase family 1 member C3, amiloride-sensitive amine oxidase, death-associated protein kinase 2 and tryptophan-tRNA ligase, that may all play a crucial role in its observed anticancer effects. Moreover, our inverse docking results showed that curcumin potentially binds also to the proteins cAMP-specific 3′,5′-cyclic phosphodiesterase 4D and 17-β-hydroxysteroid dehydrogenase type 10, which provides a new explanation for its efficiency in the treatment of Alzheimer’s disease. We firmly believe that our computational results will complement and direct future experimental studies on curcumin’s anticancer activity as well as on its therapeutic effects against Alzheimer’s disease.

APA, Harvard, Vancouver, ISO, and other styles

16

Quintanar-Audelo, Martina, Permeen Yusoff, Saravanan Sinniah, Sumana Chandramouli, and Graeme R. Guy. "Sprouty-related Ena/Vasodilator-stimulated Phosphoprotein Homology 1-Domain-containing Protein (SPRED1), a Tyrosine-Protein Phosphatase Non-receptor Type 11 (SHP2) Substrate in the Ras/Extracellular Signal-regulated Kinase (ERK) Pathway." Journal of Biological Chemistry 286, no. 26 (April 29, 2011): 23102–12. http://dx.doi.org/10.1074/jbc.m110.212662.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Wang, Hao, Stephan Lindsey, Iwona Konieczna, Elizabeth Horvath, Ling Bei, Weiqi Huang, and Elizabeth A. Eklund. "Constitutive Activation of SHP2 Protein Tyrosine Phosphatase Cooperates with HoxA10 Overexpression for Progression to Acute Myeloid Leukemia in a Murine Model." Blood 112, no. 11 (November 16, 2008): 752. http://dx.doi.org/10.1182/blood.v112.11.752.752.

Full text

Abstract:

Abstract HOX genes encode highly conserved homeodomain (HD) transcription factors and are arranged in four groups (A–D). During definitive hematopoiesis, HOX gene expression is activated 3′ to 5′ through each group. Therefore, HOX1-4 are actively transcribed in hematopoietic stem cells and HOX7-11 in committed progenitors. Under normal conditions, HoxA7-11 expression decreases during CD34+ to CD34− maturation. Abnormal Hox expression is characteristic of several poor prognosis subtypes of Acute Myeloid Leukemia (AML) including AML with translocations or duplications of the MLL gene. In such leukemias, expression of HoxB3, B4 and A7-11 is sustained in CD34−CD38+ cells. In murine bone marrow transplantation experiments, expression of MLL fusion proteins, HoxA9 or HoxA10 induces a myeloproliferative disorder (MPD) characterized by increased neutrophils (PMN). Over time, the mice progress to AML with circulating myeloid blasts. These results suggest overexpression of HoxA9 or HoxA10 is adequate for MPD, but differentiation block (AML) requires additional lesions. We found that HoxA9 and HoxA10 proteins not only decrease in expression during the CD34+ to CD34− transition, but also are tyrosine phosphorylated. In additional studies, we found that HoxA10 tyrosine phosphorylation state is relevant for differentiation stage-specific target gene expression during myelopoiesis. HoxA10 represses genes encoding phagocyte effector proteins in undifferentiated myeloid cells. During myelopoiesis, phosphorylation of conserved HD-HoxA10 tyrosines decreases binding to these genes, permitting phenotypic and functional differentiation. HoxA10 activates transcription of the gene encoding Mkp2 (Dusp4) in myeloid progenitors. Decrease in HoxA10-binding to this gene as differentiation proceeds decreases transcription and renders the cells susceptible to Jnk induced apoptosis. Therefore, we hypothesized that genetic lesions which influence post translational modification might cooperate with HoxA10 overexpression to lead from MPD to AML. In myeloid progenitors, HoxA10 is maintained in a non-phosphorylated state by SHP2 protein tyrosine phosphatase. SHP2 activity decreases as differentiation proceeds. Activating mutations in SHP2 have been described in AML. We found that such activated SHP2 mutants dephosphorylate HoxA10 through out ex vivo myelopoiesis. Therefore, we investigated cooperation between these two leukemia associated abnormalities in vivo. Mice were transplanted with bone marrow overexpressing HoxA10 (or empty vector control) with or without activated SHP2 (E76K). To control for SHP2 overexpression, other mice were transplanted with bone marrow overexpressing HoxA10 and wild type SHP2. Mice transplanted with bone marrow overexpressing HoxA10 (±SHP2) developed MPD which evolved to AML over 4 mos, consistent with previous observations. However, mice transplanted with bone marrow overexpressing HoxA10 and E76K SHP2 developed AML within 4 wks. This rapid development of AML correlated with abnormalities in expression of myeloid specific HoxA10 target genes. These studies indicate the importance of HoxA10 post translational modification for physiologically relevant function and identify cooperating lesions which may be significant for disease progression in human AML.

APA, Harvard, Vancouver, ISO, and other styles

18

Gunawardana, Jay, Fong Chun Chan, Adele Telenius, Bruce W. Woolcock, Robert Kridel, King L. Tan, Susana Ben Neriah, et al. "Protein Tyrosine Phosphatase Type-1 (PTPN1) Is Frequently Mutated In Primary Mediastinal B Cell Lymphoma and Hodgkin Lymphoma." Blood 122, no. 21 (November 15, 2013): 242. http://dx.doi.org/10.1182/blood.v122.21.242.242.

Full text

Abstract:

Abstract Introduction Hodgkin Lymphoma (HL) accounts for 11% of all lymphomas and despite being one of the most curable lymphomas, 20% of HL patients still ultimately die of their disease. Similarly, a proportion of cases of primary mediastinal B cell lymphoma (PMBCL) have refractory disease or early relapse and frequently fail second-line therapy. Development of more targeted therapeutic approaches is impeded by the lack of knowledge about the mutational landscape in the cancer genomes of these lymphomas. PTPN1 is a protein tyrosine phosphatase gene that encodes the protein, PTP1B. PTP1B dephosphorylates tyrosine residues on many activated kinases to maintain cellular homeostasis. As overactive receptor kinases are critical oncogenic events in cancer, we hypothesized that constitutively active Janus kinase-Signal transducer and activation of transcription (JAK-STAT) observed in HL and PMBCL are in part due to a mutated PTPN1 gene with an impaired functional ability to dephosphorylate this constitutive signaling pathway. Methods and samples Biopsies at the time of primary diagnosis were obtained for 49 PMBCL and 30 HL patients from the British Columbia Cancer Agency, Arizona Lymphoma Repository and the Hôpital Henri Mondor Pathology Department. DNA from PMBCL samples, microdissected Hodgkin Reed Sternberg (HRS) cells and 12 lymphoma-derived cell lines were extracted for PTPN1 exonic PCR amplification (nested PCR was used for HRS cell DNA) and Sanger sequencing. PTPN1 was silenced in a HL cell line (KMH2) by lentiviral transduction of a vector expressing shRNA and confirmed by quantitative real time (qRT) PCR. Wild type and mutant PTPN1 cDNA were cloned into the mammalian expression vector pcDNA 3.1 and expressed in HEK-293 cells. Protein expression of clinical samples, silenced and expressed cells were analyzed by immunohistochemistry and western blotting. Comparisons between groups were performed using two-sample student t tests. Results After exclusion of reported single nucleotide polymorphisms (SNPs) and silent mutations, 16 PTPN1 coding sequence mutations were found in our PMBCL cohort, corresponding to 14 mutations (29%) in clinical samples and 2 in PMBCL-dervied cell lines. Twelve additional mutations were discovered in our HL cohort, corresponding to 6 mutations (20%) in HRS cell samples and another 6 in HL-derived cell lines. In total, 14 (54%) missense, 4 (15%) frameshift, 3 (12%) single amino acid deletions, 4 (15%) nonsense mutations, and 1 (4%) promoter mutation were observed. Eight of these mutations were confirmed as somatic by sequencing of matched constitutional DNA. Silencing of PTPN1 resulted in hyperphosphorylation of JAK1, JAK2, STAT3, STAT5, STAT6 and up-regulation of the oncogenes, MYC and BCL6. Ectopic expression of nonsense and missense PTPN1 mutants in HEK-293 cells led to sustained phosphorylation of STAT6 in comparison to the empty vector control (densitometric values Q9* 0.5 vs. 1.0, R156* 0.7 vs. 1.0, M74L 0.4 vs. 1.0 and M282L 0.8 vs. 1.0). Furthermore, no phosphatase activity was observed for the nonsense mutants and moderate phosphatase activity for the missense mutants using a tyrosine phosphatase-specific substrate (fold change Q9* 2.0, R156* 1.9, M74L 46.7, M282L 46.0 and WT 58.3, compared to empty vector control). Immunohistochemical analysis showed that PTPN1 mutations correspond to decreased protein expression in PMBCL (p=0.03). Discussion PTPN1 is recurrently mutated in PMBCL and HL contributing to constitutive JAK-STAT signaling and oncogene dysregulation. These data suggest PTPN1 mutations as novel driver alterations in these lymphomas and might provide a novel, rational therapeutic target for treating HL and PMBCL patients. Disclosures: Savage: Eli-Lilly: Consultancy. Connors:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding.

APA, Harvard, Vancouver, ISO, and other styles

19

Li, Kang, Luobu Gesang, Zeng Dan, and Lamu Gusang. "Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways." Oxidative Medicine and Cellular Longevity 2016 (2016): 1–13. http://dx.doi.org/10.1155/2016/6967396.

Full text

Abstract:

The molecular mechanisms for hypoxic environment causing the injury of intestinal mucosal barrier (IMB) are widely unknown. To address the issue, Han Chinese from 100 m altitude and Tibetans from high altitude (more than 3650 m) were recruited. Histological and transcriptome analyses were performed. The results showed intestinal villi were reduced and appeared irregular, and glandular epithelium was destroyed in the IMB of Tibetans when compared with Han Chinese. Transcriptome analysis revealed 2573 genes with altered expression. The levels of 1137 genes increased and 1436 genes decreased in Tibetans when compared with Han Chinese. Gene ontology (GO) analysis indicated most immunological responses were reduced in the IMB of Tibetans when compared with Han Chinese. Gene microarray showed that there were 25-, 22-, and 18-fold downregulation for growth factor receptor-bound protein 2 (GRB2), epidermal growth factor receptor (EGFR), and tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) in the IMB of Tibetans when compared with Han Chinese. The downregulation of EGFR, GRB2, and PTPN11 will reduce the production of reactive oxygen species and protect against oxidative stress-induced injury for intestine. Thus, the transcriptome analysis showed the protecting functions of IMB patients against hypoxia-induced oxidative injury in the intestine of Tibetans via affecting GRB2/EGFR/PTPN11 pathways.

APA, Harvard, Vancouver, ISO, and other styles

20

Fobare, Sydney, Jessica Kohlschmidt, Hatice Gulcin Ozer, Krzysztof Mrózek, Deedra Nicolet, Alice S. Mims, Ramiro Garzon, et al. "Molecular, clinical, and prognostic implications of PTPN11 mutations in acute myeloid leukemia." Blood Advances 6, no. 5 (February 25, 2022): 1371–80. http://dx.doi.org/10.1182/bloodadvances.2021006242.

Full text

Abstract:

Abstract Prognostic factors associated with chemotherapy outcomes in patients with acute myeloid leukemia (AML) are extensively reported, and one gene whose mutation is recognized as conferring resistance to several newer targeted therapies is protein tyrosine phosphatase non-receptor type 11 (PTPN11). The broader clinical implications of PTPN11 mutations in AML are still not well understood. The objective of this study was to determine which cytogenetic abnormalities and gene mutations co-occur with PTPN11 mutations and how PTPN11 mutations affect outcomes of patients treated with intensive chemotherapy. We studied 1725 patients newly diagnosed with AML (excluding acute promyelocytic leukemia) enrolled onto the Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology trials. In 140 PTPN11-mutated patient samples, PTPN11 most commonly co-occurred with mutations in NPM1, DNMT3A, and TET2. PTPN11 mutations were relatively common in patients with an inv(3)(q21q26)/t(3;3)(q21;q26) and a normal karyotype but were very rare in patients with typical complex karyotype and core-binding factor AML. Mutations in the N-terminal SH2 domain of PTPN11 were associated with a higher early death rate than those in the phosphatase domain. PTPN11 mutations did not affect outcomes of NPM1-mutated patients, but these patients were less likely to have co-occurring kinase mutations (ie, FLT3-ITD), suggesting activation of overlapping signaling pathways. However, in AML patients with wild-type NPM1, PTPN11 mutations were associated with adverse patient outcomes, providing a rationale to study the biology and treatment approaches in this molecular group. This trial was registered at www.clinicaltrials.gov as #NCT00048958 (CALGB 8461), #NCT00899223 (CALGB 9665), and #NCT00900224 (CALGB 20202).

APA, Harvard, Vancouver, ISO, and other styles

21

Papp, Michael, Xiaopeng Li, Jiaju Zhuang, Rongqi Wang, and Bruce D. Uhal. "Angiotensin receptor subtype AT1 mediates alveolar epithelial cell apoptosis in response to ANG II." American Journal of Physiology-Lung Cellular and Molecular Physiology 282, no. 4 (April 1, 2002): L713—L718. http://dx.doi.org/10.1152/ajplung.00103.2001.

Full text

Abstract:

Previous work from this laboratory demonstrated induction of apoptosis in lung alveolar epithelial cells (AEC) by purified angiotensin II (ANG II) and expression of mRNAs for both ANG II receptor subtypes AT1 and AT2(Wang R, Zagariya A, Ibarra-Sunga O, Gidea C, Ang E, Deshmukh S, Chaudhary G, Baraboutis J, Filippatos G, and Uhal BD. Am J Physiol Lung Cell Mol Physiol 276: L885–L889, 1999.). The present study was designed to determine the ANG II receptor subtype mediating AEC apoptosis in response to ANG II. Apoptosis was induced with purified ANG II applied to the human lung AEC-derived carcinoma cell line A549 or to primary AEC isolated from Wistar rats. In both cell types, the AT1-selective receptor antagonists L-158809 or losartan inhibited ANG II-induced apoptosis by 90% at concentrations of 10−8 M and 10−7 M, respectively. The inhibition was concentration dependent with IC50 of 10−12 M and 10−11 M on the primary rat AEC. In contrast, the AT2-selective antagonists PD-123319 or PD-126055 could not block ANG II-induced apoptosis in either cell type. In primary rat AEC, apoptosis in response to ANG II was blunted in a dose-dependent manner by the protein kinase C inhibitor chelerythrine but not by the tyrosine phosphatase inhibitor sodium orthovanadate. Together, these data indicate that AEC apoptosis in response to ANG II is mediated by receptor subtype AT1, despite the expression of mRNAs for both AT1 and AT2.

APA, Harvard, Vancouver, ISO, and other styles

22

Peng, Xiandong, Min Yu, and Jiazhou Chen. "Transcriptome sequencing identifies genes associated with invasion of ovarian cancer." Journal of International Medical Research 48, no. 9 (September 2020): 030006052095091. http://dx.doi.org/10.1177/0300060520950912.

Full text

Abstract:

Objective To identify key genes in ovarian cancer using transcriptome sequencing in two cell lines: MCV152 (benign ovarian epithelial tumour) and SKOV-3 (ovarian serous carcinoma). Methods Differentially expressed genes (DEGs) between SKOV-3 and MCV152 were identified. Candidate genes were assessed for enrichment in gene ontology function and Kyoto Encyclopaedia of Genes and Genomes pathway. Candidate gene expression in SKOV-3 and MCV152 cells was validated using Western blots. Results A total of 2020 upregulated and 1673 downregulated DEGs between SKOV3 and MCV152 cells were identified that were significantly enriched in the cell adhesion function. Upregulated DEGs, such as angiopoietin 2 ( ANGPT2), CD19 molecule ( CD19), collagen type IV alpha 3 chain ( COL4A3), fibroblast growth factor 18 ( FGF18), integrin subunit beta 4 ( ITGB4), integrin subunit beta 8 ( ITGB8), laminin subunit alpha 3 ( LAMA3), laminin subunit gamma 2 ( LAMC2), protein phosphatase 2 regulatory subunit Bgamma ( PPP2R2C) and spleen associated tyrosine kinase ( SYK) were significantly involved in the extracellular matrix-receptor interaction pathway. Downregulated DEGs, such as AKT serine/threonine kinase 3 ( AKT3), collagen type VI alpha 1 chain ( COL6A1), colony stimulating factor 3 ( CSF3), fibroblast growth factor 1 ( FGF1), integrin subunit alpha 2 ( ITGA2), integrin subunit alpha 11 ( ITGA11), MYB proto-oncogene, transcription factor ( MYB), phosphoenolpyruvate carboxykinase 2, mitochondrial ( PCK2), placental growth factor ( PGF), phosphoinositide-3-kinase adaptor protein 1 ( PIK3AP1), serum/glucocorticoid regulated kinase 1 ( SGK1), toll like receptor 4 ( TLR4) and tumour protein p53 ( TP53) were involved in PI3K-Akt signalling. Expression of these DEGs was confirmed by Western blot analyses. Conclusion Candidate genes enriched in cell adhesion, extracellular matrix–receptor interaction and PI3K-Akt signalling pathways were identified that may be closely associated with ovarian cancer invasion and potential targets for ovarian cancer treatment.

APA, Harvard, Vancouver, ISO, and other styles

23

Binder, G., K. Neuer, M. B. Ranke, and N. E. Wittekindt. "PTPN11 Mutations Are Associated with Mild Growth Hormone Resistance in Individuals with Noonan Syndrome." Journal of Clinical Endocrinology & Metabolism 90, no. 9 (September 1, 2005): 5377–81. http://dx.doi.org/10.1210/jc.2005-0995.

Full text

Abstract:

Abstract Context: Noonan syndrome is frequently associated with an unclear disturbance of GH secretion. Half the individuals with Noonan syndrome carry a heterozygous mutation of the nonreceptor-type protein tyrosine phosphatase, Src homology region 2-domain phosphatase-2 (SHP-2), encoded by PTPN11, which has a role in GH receptor signaling. Objective: The objective of this study was to compare GH secretion and IGF-I/IGF-binding protein-3 (IGFBP-3) levels of the SHP-2 mutation-positive (mut+ group) vs. mutation-negative individuals (mut− group). Design, Setting, and Patients: All children presenting to us with short stature plus at least three typical anomalies of Noonan syndrome or pulmonic stenosis during the last 5 yr (n = 29; 10 females and 19 males) were recruited. Auxological data, dysmorphic features, and cardiac morphology were documented. Hormone levels were measured by RIA. All coding exons of PTPN11 were sequenced after PCR amplification. Intervention: A prepubertal subgroup (n = 11) was treated with recombinant human GH (rhGH) to promote growth. Results: Sequencing yielded 11 different PTPN11 missense mutations in 16 of the 29 patients (55% mut+). Pulmonic stenosis (81 vs. 15%; P = 0.0007) and septal defects (63 vs. 15%; P = 0.02) were more frequently found in the mut+ group, whereas minor anomalies, cryptorchidism, and learning disabilities were as frequent in the mut+ group as in the mut− group. The mut+ group was younger at presentation (mean ± sd, 5.1 ± 2.7 vs. 10.3 ± 5.2 yr; P = 0.002), but not significantly shorter [−3.15 ± 0.92 vs. −3.01 ± 1.35 height sd score (SDS)]. IGF-I levels (−2.03 ± 0.69 vs. −1.13 ± 0.89 SDS; P = 0.005) and IGFBP-3 levels (−0.92 ± 1.26 vs. 0.40 ± 1.08 SDS; P = 0.006) were significantly lower in the mut+ group. In contrast, GH levels showed a tendency to be higher in the mut+ group during spontaneous secretion at night and arginine stimulation (P ≥ 0.075, not significant). The mean change in height SDS after 1 yr of rhGH therapy (0.043 mg/kg·d) was +0.66 ± 0.21 in the mut+ group (n = 8), but +1.26 ± 0.36 in the mut− group (n = 3; P = 0.007). Conclusions: Our data suggest that SHP-2 mutations in Noonan syndrome cause mild GH resistance by a postreceptor signaling defect, which seems to be partially compensated for by elevated GH secretion. This defect may contribute to the short stature phenotype in children with SHP-2 mutations and their relatively poor response to rhGH.

APA, Harvard, Vancouver, ISO, and other styles

24

Shafaee, Maryam Nemati, Kristen Otte, Nicholas J. Neill, Kent C. Osborne, Thomas F. Westbrook, Susan Hilseneck, and Matthew J. Ellis. "Abstract OT2-28-01: A phase 2 study of sitravatinib in metastatic, pre-treated, triple negative breast cancer, NCT # 04123704." Cancer Research 82, no. 4_Supplement (February 15, 2022): OT2–28–01—OT2–28–01. http://dx.doi.org/10.1158/1538-7445.sabcs21-ot2-28-01.

Full text

Abstract:

Abstract Background:Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, disproportionally affecting African American and Hispanic patients, and germline BRCA1/2 mutation carriers. Prognosis of relapsed, metastatic disease is extremely poor and effective well-tolerated therapies are urgently needed. Our collaborators have discovered that TNBCs often lose feedback control of receptor tyrosine kinases (RTKs) including PDGFR and MET, locking these receptors in a chronically active state. These receptors share a common negative regulator called Protein Tyrosine Phosphatase, Non-Receptor Type 12 (PTPN12). Baylor investigators have shown that PTPN12- deficient TNBCs may be responsive to combined RTK inhibition. Sitravatinib is a spectrum selective RTK inhibitor that has shown strong antitumor activity in patient derived xenografts (PDXs) of TNBC with low levels of PTPN12. We have therefore designed a phase II, multi-institution, two cohort trials to evaluate the efficacy of sitravatinib in patients with metastatic TNBC (mTNBC). Methods: Patients with diagnosis of mTNBC who have received at least one line of chemotherapy +/- atezolizumab for advanced disease would be considered for enrollment. Patients would need to have tissue from metastatic site available for evaluation or agree to undergo biopsy if banked tumor tissue is not available. Sitravatinib at 100 mg daily, the recommended phase 2 dose for sitravatinib monotherapy, will be started at the initiation of the study and continued until progression or unacceptable toxicity. The study will employ a modified optimal Simon’s two stage design. Patients will be recruited into two cohorts: PTPN12 low or PTPN12 high/normal cohorts simultaneously and independently. Seven patients will be enrolled to each arm during the first stage. After the first stage, depending on the observed number of responses, the study will proceed to the 2nd stage. The primary endpoint is progression-free survival status at 24 weeks (PFS24). Current Trial status: The trial is funded by Mirati Therapeutics and opened to enrollment at Dan L Duncan Comprehensive Cancer Center (DLDCCC) clinics as of 6/8/21. Trial is due to open at UT Southwestern Dallas by 11/2021. The correlative science is funded by an institutional SPORE grant. Conclusion: This trial aims to show that sitravatinib is safe and to investigate whether it could be a treatment option in mTNBC. Citation Format: Maryam Nemati Shafaee, Kristen Otte, Nicholas J Neill, Kent C Osborne, Thomas F Westbrook, Susan Hilseneck, Matthew J Ellis. A phase 2 study of sitravatinib in metastatic, pre-treated, triple negative breast cancer, NCT # 04123704 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-28-01.

APA, Harvard, Vancouver, ISO, and other styles

25

Spina, Valeria, Hossein Khiabanian, Alessio Bruscaggin, Monica Messina, Sara Monti, Antony B. Holmes, Sabina Chiaretti, et al. "The Coding Genome of Nodal Marginal Zone Lymphoma Reveals Recurrent Molecular Alterations of PTPRD and Other Jak/Stat Signaling Genes." Blood 124, no. 21 (December 6, 2014): 705. http://dx.doi.org/10.1182/blood.v124.21.705.705.

Full text

Abstract:

Abstract Background. Nodal marginal zone lymphoma (NMZL) is one of the few B-cell tumors still remaining orphan of cancer gene lesions. By combining whole exome sequencing (WES), deep sequencing of tumor-related genes, high resolution SNP array and RNAseq, here we aim at characterizing the coding genome of NMZL and at disclosing the pathways that are molecularly deregulated in this lymphoma. Methods. The study was based on 35 NMZL (tumor representation >70%) with a diagnosis confirmed by: i) pathological revision of lymph node histology; and ii) lack of clinico-radiological evidence of extranodal or splenic disease either at diagnosis or during follow-up. Consistent with NMZL, the cases investigated: i) lacked CD5, CD10 and cyclin D1 expression, 7q deletion, t(11;14), t(14;18), t(11;18) and t(1;14) translocations; and ii) recurrently harbored +3 (14%), +12 (14%) and preferential usage of the IGHV4-34 gene (17%). WES (HiSeq 2500, Illumina; mean coverage per sample: 38x-114x) and high density SNP array (Cytoscan HD, Affymetrix) of tumor/normal DNA pairs from 18 discovery NMZL identified 557 non-synonymous somatic mutations (average: 30.9/case) affecting 504 genes and 61 copy number abnormalities (CNA) (average 3.4/case). To further characterize mutation recurrence, the 504 discovered genes were investigated in an independent validation panel of 17 NMZL by targeted sequencing of tumor/normal DNA pairs (MiSeq; target region: 1.6 Mb; mean coverage per sample: 171x-386x). The 17 validation NMZL were also assessed for CNA by high density SNP arrays. RNAseq of 11 discovery NMZL did not identify any recurrent gene fusion. Results. By compiling the results of WES and high resolution SNP array, 39 genes were recurrently affected in >3/35 (9%) NMZL by mutations (n=30 genes) or focal CNA (n=9 genes). Among these, MLL2 (34%), PTPRD (20%) and NOTCH2 (20%) were most frequently mutated. Overall, recurrently mutated genes pointed to the molecular deregulation of specific programs in NMZL, namely JAK/STAT, NOTCH, NF-κB and toll-like receptor (TLR) signaling, cell cycle, chromatin remodeling/transcriptional regulation and immune escape (Fig. 1A). JAK/STAT signaling was targeted by mutually exclusive lesions in 43% of NMZL, and the protein tyrosine phosphatase receptor delta (PTPRD) tumor suppressor was the most frequently affected gene of this system in 20% of NMZL (Fig. 1B-E). PTPRD inhibits JAK/STAT signaling through the dephosphorylation of active p-STAT3. PTPRD lesions in NMZL were represented by somatic mutations that truncated or modified the tyrosine phosphatase domain, as well as deletions of the entire gene locus, including focal and biallelic losses (Fig. 1B-C). Interrogation of institutional and public genomic datasets revealed that PTPRD mutations are specific for NMZL, being rare or absent in other mature B-cell tumors, including splenic marginal zone lymphoma (Fig. 1D). Other JAK/STAT signaling genes affected in NMZL were JAK2, CXCR4 (6%), PTPN2, JAK3, STAT2, SH2B3 and CUL3 (3%) (Fig. 1E). NF-kB signaling was altered in 54% of NMZL by lesions of TNFAIP3 (14%), BCL10, REL (11%), CARD11 (9%), TRAF3 and BIRC3 (6%). NOTCH signaling was targeted in 40% of NMZL by mutations that alternatively involved NOTCH2 (20%), SPEN (11%), RBPJL (6%), FBXW7, DTX1, ITCH and MAML2 (3%). TLR signaling was targeted in 17% of NMZL, including mutations of MYD88 (9%), IRAK1BP1, PELI2 and SEMP6 (3%). Several cell cycle genes were molecularly deregulated in 43% of NMZL, including CDKN2A, PARK2, PARKG (9%), CDC16, CDCA2 (6%), CCNA1, CCNT2, CDK5, CDK13, CDK20, BTG2, HECA and PLK2 (3%). Most (71%) NMZL harbored genetic lesions affecting epigenetic modifiers (MLL2: 34%; CREBBP: 9%; EP300: 6%; TRRAP: 6%), histones (20%) or transcriptional co-repressors (TBL1XR1: 14%; ARID1A: 14%; RCOR1: 11%; NCOR2: 9%, ARID1B: 9%). Finally, the TNFRSF14 and FAS genes, involved in T cell-mediated tumor surveillance, were disrupted by mutations and/or deletions in 17% and 14% NMZL, respectively. Conclusions. A number of actionable cellular programs are molecularly deregulated in NMZL, including JAK/STAT, NOTCH, NF-κB and TLR signaling, cell cycle and chromatin remodeling. PTPRD lesions are among the most recurrent alterations in NMZL and appear to be specific for this lymphoma type across mature B-cell tumors. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

APA, Harvard, Vancouver, ISO, and other styles

26

Kobayashi, Michihiro, Yunpeng Bai, Sisi Chen, Sarah C. Nabinger, Chonghua Yao, Zhong-Yin Zhang, and Yan Liu. "PRL2 Phosphatase Is a Key Mediator of Oncogenic Cytokine Signaling in Leukemia Stem Cells." Blood 128, no. 22 (December 2, 2016): 724. http://dx.doi.org/10.1182/blood.v128.22.724.724.

Full text

Abstract:

Abstract Acute myeloid leukemia (AML) is a heterogeneous disease with multiple signaling pathways contributing to its pathogenesis. Mutations in receptor tyrosine kinase KIT and FLT3 are found in approximately 40% of AML patients and targeted therapies for inhibiting KIT and FLT3 have failed, thus new targets for therapeutic intervention need to be identified. The phosphatase of regenerating liver (PRL) family of phosphatases, consisting of PRL1, PRL2, and PRL3, represents an intriguing group of proteins being validated as biomarkers and therapeutic targets in human cancer. While PRL2 is highly expressed in some subtypes of human AML, including AML1-ETO+ AML and AML with mixed lineage leukemia (MLL) translocations, its role in AML is largely unknown. To determine the role of PRL2 in the pathogenesis of AML, we utilized two murine models of human AML induced by transducing mouse HSCs with AML1-ETO or MLL-AF9. We found that PRL2 is important for the progression and maintenance of leukemia induced by AML1-ETO or MLL-AF9 through enhancing leukemia stem cell (LSC) self-renewal. To elucidate the mechanisms by which PRL2 promotes LSC maintenance, we performed genome wide RNA-seq analysis of MLL-AF9+ LSCs. Gene Set Enrichment Analysis (GESA) indicates that PRL2 deficiency alters the MLL-AF9 signature essential for LSC self-renewal. We have recently identified PRL2 to be important for the proliferation and self-renewal of hematopoietic stem cells (HSCs) through the regulation of KIT signaling. Notably, PRL2 null hematopoietic progenitor cells showed decreased KIT phosphorylation as well as ERK phosphorylation following SCF stimulation, suggesting that PRL2 is important for KIT activation. Given that KIT inactivation could be mediated by removal from the cell surface and intracellular degradation, we reasoned that PRL2 may regulate KIT receptor internalization and stability. That was indeed the case. We found that the KIT protein half-life in PRL2 null hematopoietic progenitor cells (Kit+) was significantly decreased compared to WT cells. Furthermore, PRL2 null progenitor cells showed enhanced KIT ubiquitination compared to WT cells and less KIT was found on the surface of PRL2 null progenitor cells compared to WT cells following SCF stimulation. We also found that loss of PRL2 in human AML cells resulted in enhanced internalization of KIT. These observations demonstrate that PRL2 deficiency results in less KIT on the cell surface and a lower global KIT level in the cell. Upon SCF stimulation, KIT binds to and induces the phosphorylation of CBL proteins, which in turn act as E3 ligases, mediating the ubiquitination and degradation of KIT. To understand how PRL2 modulates the turnover of KIT in hematopoietic cells, we performed GST-pulldown assays and found that the substrate-trapping mutant PRL2/CS-DA showed an increased association with KIT and CBL compared to wild-type PRL2 in Kasumi-1 cells, suggesting that KIT and CBL may be PRL2 substrates. Furthermore, we found that PRL2/CS-DA mutant showed enhanced association with FLT3 and CBL compared to wild-type PRL2 in MV4-11 cells. Our data suggest that PRL2 dephosphorylates CBL and inhibits CBL activity toward KIT and FLT3, leading to sustained activation of downstream signaling pathways. To determine the functional significance of PRL2 in human AML with KIT and FLT3 mutations, we utilized two well-established murine model of myeloproliferative neoplasms (MPN) induced by KITD814V or FLT3-ITD. We found that loss of Prl2 decreased the ability of oncogenic KITD814V and FLT3-ITD to promote mouse hematopoietic stem and progenitor cell (HSPC) proliferation in vitro andthe development of MPN in vivo. Furthermore, we found that genetic and pharmacological inhibition of PRL2 decreased the proliferation and survival of human AML cells bearing KIT or FLT3 mutations. Taken together, we demonstrate that PRL2 promotes leukemia stem cell (LSC) self-renewal and maintenance through sustaining the activity of oncogenic KIT and FLT3 signals. Our findings suggest that pharmacological inhibition of PRL2 holds potential as a novel therapy for acute myeloid leukemia, and might also be applicable to the treatment of other human cancers. Disclosures No relevant conflicts of interest to declare.

APA, Harvard, Vancouver, ISO, and other styles

27

Spalinger, Marianne R. "Protein tyrosine phosphatase non-receptor type 2 and inflammatory bowel disease." World Journal of Gastroenterology 22, no. 3 (2016): 1034. http://dx.doi.org/10.3748/wjg.v22.i3.1034.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Chao, Hsin-Chih Albert, Chia-Ling Chung, Hsien-An Pan, Pao-Chi Liao, Pao-Lin Kuo, and Chao-Chin Hsu. "Protein tyrosine phosphatase non-receptor type 14 is a novel sperm-motility biomarker." Journal of Assisted Reproduction and Genetics 28, no. 9 (June 24, 2011): 851–61. http://dx.doi.org/10.1007/s10815-011-9602-0.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Rani, Rajni, Anamika Singh, Neetu Israni, Archana Singh, Pankaj Sharma, and Hemant K. Kar. "The Role of Polymorphic Protein Tyrosine Phosphatase Non-Receptor Type 22 in Leprosy." Journal of Investigative Dermatology 129, no. 11 (November 2009): 2726–28. http://dx.doi.org/10.1038/jid.2009.140.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Kim, Mihwa, Liza Morales, Ik-Soon Jang, Yong-Yeon Cho, and Dae Kim. "Protein Tyrosine Phosphatases as Potential Regulators of STAT3 Signaling." International Journal of Molecular Sciences 19, no. 9 (September 11, 2018): 2708. http://dx.doi.org/10.3390/ijms19092708.

Full text

Abstract:

The signal transducer and activator of transcription 3 (STAT3) protein is a major transcription factor involved in many cellular processes, such as cell growth and proliferation, differentiation, migration, and cell death or cell apoptosis. It is activated in response to a variety of extracellular stimuli including cytokines and growth factors. The aberrant activation of STAT3 contributes to several human diseases, particularly cancer. Consequently, STAT3-mediated signaling continues to be extensively studied in order to identify potential targets for the development of new and more effective clinical therapeutics. STAT3 activation can be regulated, either positively or negatively, by different posttranslational mechanisms including serine or tyrosine phosphorylation/dephosphorylation, acetylation, or demethylation. One of the major mechanisms that negatively regulates STAT3 activation is dephosphorylation of the tyrosine residue essential for its activation by protein tyrosine phosphatases (PTPs). There are seven PTPs that have been shown to dephosphorylate STAT3 and, thereby, regulate STAT3 signaling: PTP receptor-type D (PTPRD), PTP receptor-type T (PTPRT), PTP receptor-type K (PTPRK), Src homology region 2 (SH-2) domain-containing phosphatase 1(SHP1), SH-2 domain-containing phosphatase 2 (SHP2), MEG2/PTP non-receptor type 9 (PTPN9), and T-cell PTP (TC-PTP)/PTP non-receptor type 2 (PTPN2). These regulators have great potential as targets for the development of more effective therapies against human disease, including cancer.

APA, Harvard, Vancouver, ISO, and other styles

31

Kim, Jin Soo, Ok Ran Shin, Hyung Keun Kim, Young Seok Cho, Chang Hyeok An, Keun Woo Lim, and Sung Soo Kim. "Overexpression of Protein Phosphatase Non-receptor Type 11 (PTPN11) in Gastric Carcinomas." Digestive Diseases and Sciences 55, no. 6 (August 19, 2009): 1565–69. http://dx.doi.org/10.1007/s10620-009-0924-z.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Spalinger, Marianne R., and Michael Scharl. "The role for protein tyrosine phosphatase non-receptor type 22 in regulating intestinal homeostasis." United European Gastroenterology Journal 4, no. 3 (August 6, 2015): 325–32. http://dx.doi.org/10.1177/2050640615600115.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Spalinger, Marianne R., Silvia Lang, Stephan R. Vavricka, Michael Fried, Gerhard Rogler, and Michael Scharl. "Protein Tyrosine Phosphatase Non-Receptor Type 22 Modulates NOD2-Induced Cytokine Release and Autophagy." PLoS ONE 8, no. 8 (August 26, 2013): e72384. http://dx.doi.org/10.1371/journal.pone.0072384.

Full text

APA, Harvard, Vancouver, ISO, and other styles

34

Spalinger, Marianne R., Thomas S. B. Schmidt, Marlene Schwarzfischer, Larissa Hering, Kirstin Atrott, Silvia Lang, Claudia Gottier, et al. "Protein tyrosine phosphatase non-receptor type 22 modulates colitis in a microbiota-dependent manner." Journal of Clinical Investigation 129, no. 6 (May 20, 2019): 2527–41. http://dx.doi.org/10.1172/jci123263.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Chang, Hui-Hsin, William Tseng, Jing Cui, Karen Costenbader, and I.-Cheng Ho. "Altered expression of protein tyrosine phosphatase, non-receptor type 22 isoforms in systemic lupus erythematosus." Arthritis Research & Therapy 16, no. 1 (2014): R14. http://dx.doi.org/10.1186/ar4440.

Full text

APA, Harvard, Vancouver, ISO, and other styles

36

Spalinger, Marianne R., Stephanie Kasper, Claudia Gottier, Isabelle Frey-Wagner, Silvia Lang, Kirstin Atrott, Stephan R. Vavricka, et al. "125 Protein Tyrosine Phosphatase Non-Receptor Type 22 Dephosphorylates NLRP3 to Enable Efficient Inflammasome Activation." Gastroenterology 148, no. 4 (April 2015): S—33. http://dx.doi.org/10.1016/s0016-5085(15)30114-1.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Adel, Sherihan, Amal Mansour, Manal Louka, M. Matboli, S. F. Elmekkawi, and Nahed Swelam. "Evaluation of MicroRNA-210 and Protein tyrosine phosphatase, non-receptor type 2 in Pre-eclampsia." Gene 596 (January 2017): 105–9. http://dx.doi.org/10.1016/j.gene.2016.10.014.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Zhang, Dongjiao, Yanfei Jiang, Dawei Song, Zhenkun Zhu, Cong Zhou, Li Dai, and Xin Xu. "Tyrosine‐protein phosphatase non‐receptor type 2 inhibits alveolar bone resorption in diabetic periodontitis via dephosphorylating CSF1 receptor." Journal of Cellular and Molecular Medicine 23, no. 10 (August 2, 2019): 6690–99. http://dx.doi.org/10.1111/jcmm.14545.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Kasper, Stephanie H., Marianne R. Spalinger, Tina Raselli, and Michael Scharl. "A Cell Type-Specific Role of Protein Tyrosine Phosphatase Non-Receptor Type 2 in Regulating ER Stress Signalling." Digestion 91, no. 3 (March 25, 2015): 248–56. http://dx.doi.org/10.1159/000375459.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Nandi, Sisir, and Mridula Saxena. "Potential Inhibitors of Protein Tyrosine Phosphatase (PTP1B) Enzyme: Promising Target for Type-II Diabetes Mellitus." Current Topics in Medicinal Chemistry 20, no. 29 (November 20, 2020): 2692–707. http://dx.doi.org/10.2174/1568026620999200904121432.

Full text

Abstract:

Background: There has been growing interest in the development of highly potent and selective protein tyrosine phosphatase (PTP1B) inhibitors for the past 2-3 decades. Though most PTPs share a common active site motif, the interest in selective inhibitors, particularly against PTP1B is increasing to discover new chemical entities as antidiabetic agents. In the current paradigm to find potent and selective PTP1B inhibitors, which is currently considered as one of the best validated biological targets for non-insulin-dependent diabetic and obese individuals, resistance to insulin due to decreased sensitivity of the insulin receptor is a pathological factor and is also genetically linked, causing type II diabetes. Objectives: Insulin receptor sensitization is performed by a signal transduction mechanism via a selective protein tyrosine phosphatase (PTP1B). After the interaction of insulin with its receptor, autophosphorylation of the intracellular part of the receptor takes place, turning it into an active kinase (sensitization). PTP1B is involved in the desensitization of the receptor by dephosphorylation. PTP1b inhibitors delay the receptor desensitization, prolonging insulin effect and making PTP1B as a drug target for the treatment of diabetes II. Therefore, it has become a major target for the discovery of potent drugs for the treatment of type II diabetes and obesity. An attempt has been made in the present study to discuss the latest design and discovery of protein tyrosine phosphatase (PTP1B) inhibitors. Methods: Many PTP1B inhibitors such as diaminopyrroloquinazoline, triazines, pyrimido triazine derivatives, 2-(benzylamino)-1-phenylethanol, urea, acetamides and piperazinylpropanols, phenylsulphonamides and phenylcarboxamide, benzamido, arylcarboxylic acid derivatives, arylsupfonyl derivatives, thiazoles, isothiozolidiones and thiazolodinones have been discussed, citing the disease mechanisms. Results: The reader will gain an overview of the structure and biological activity of recently developed PTPs inhibitors. Conclusion: The co-crystallized ligands and the screened inhibitors could be used as a template for the further design of potent congeners.

APA, Harvard, Vancouver, ISO, and other styles

41

Elamin, Yasir, Sinead Toomey, Aoife Carr, Kenneth O'Byrne, Shereen Rafee, Kathy Gately, Oscar S. Breathnach, et al. "The role of protein tyrosine phosphatase non-receptor 11 (PTPN11) mutations in lung squamous cell carcinoma (SQCC)." Journal of Clinical Oncology 32, no. 15_suppl (May 20, 2014): e22174-e22174. http://dx.doi.org/10.1200/jco.2014.32.15_suppl.e22174.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Selvakumar, Ponniah, and Rajendra K. Sharma. "Phosphorylation and dephosphorylation of human myristoyltransferase type 1This paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference." Canadian Journal of Physiology and Pharmacology 84, no. 7 (July 2006): 707–12. http://dx.doi.org/10.1139/y06-004.

Full text

Abstract:

N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the co-translational and (or) post-translational transfer of myristate to the amino terminal glycine residue of a number of important proteins, especially the non-receptor tyrosine kinases whose activity is important for tumorigenesis. Human NMT was found to be phosphorylated by non-receptor tyrosine kinase family members of Lyn, Fyn, and Lck and dephosphorylated by the Ca2+/calmodulin-dependent protein phosphatase, calcineurin. In this review, we discuss the cross-talk that exists between NMT and their N-myristoylated protein substrates. The cross-talk among NMT, tyrosine kinases, and phosphatases may be determined by their subcellular localization and by the physiological state of the cell.

APA, Harvard, Vancouver, ISO, and other styles

43

Boni, Christian, Carlo Laudanna, and Claudio Sorio. "A Comprehensive Review of Receptor-Type Tyrosine-Protein Phosphatase Gamma (PTPRG) Role in Health and Non-Neoplastic Disease." Biomolecules 12, no. 1 (January 6, 2022): 84. http://dx.doi.org/10.3390/biom12010084.

Full text

Abstract:

Protein tyrosine phosphatase receptor gamma (PTPRG) is known to interact with and regulate several tyrosine kinases, exerting a tumor suppressor role in several type of cancers. Its wide expression in human tissues compared to the other component of group 5 of receptor phosphatases, PTPRZ expressed as a chondroitin sulfate proteoglycan in the central nervous system, has raised interest in its role as a possible regulatory switch of cell signaling processes. Indeed, a carbonic anhydrase-like domain (CAH) and a fibronectin type III domain are present in the N-terminal portion and were found to be associated with its role as [HCO3−] sensor in vascular and renal tissues and a possible interaction domain for cell adhesion, respectively. Studies on PTPRG ligands revealed the contactins family (CNTN) as possible interactors. Furthermore, the correlation of PTPRG phosphatase with inflammatory processes in different normal tissues, including cancer, and the increasing amount of its soluble form (sPTPRG) in plasma, suggest a possible role as inflammatory marker. PTPRG has important roles in human diseases; for example, neuropsychiatric and behavioral disorders and various types of cancer such as colon, ovary, lung, breast, central nervous system, and inflammatory disorders. In this review, we sum up our knowledge regarding the latest discoveries in order to appreciate PTPRG function in the various tissues and diseases, along with an interactome map of its relationship with a group of validated molecular interactors.

APA, Harvard, Vancouver, ISO, and other styles

44

Penrose, Harrison M., and Declan F. McCole. "674 Spermidine Stimulates Protein Tyrosine Phosphatase Non-Receptor Type 2-Mediated Protection of Intestinal Epithelial Barrier Function." Gastroenterology 144, no. 5 (May 2013): S—123. http://dx.doi.org/10.1016/s0016-5085(13)60441-2.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Marchelletta, Ronald R., Taylaur W. Smith, Jessica A. Bañuelos, Carli Smith, Brian Houng, Stephan Myers, and Declan F. McCole. "Tu1740 Matriptase-1 Modulation of Claudin-2 Is Protein Tyrosine Phosphatase Non-Receptor Type 2 (PTPN2) Dependent." Gastroenterology 144, no. 5 (May 2013): S—834. http://dx.doi.org/10.1016/s0016-5085(13)63103-0.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Yamasaki, A., S. Koga, S. Ichimiya, K. Nakayama, Y. Oyama, Y. Fujioka, and H. Onishi. "Protein tyrosine phosphatase non-receptor type 3 (PTPN3) could be a new therapeutic target for pancreatic cancer." Annals of Oncology 30 (October 2019): v808. http://dx.doi.org/10.1093/annonc/mdz269.037.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Scharl, Michael, Petr Hruz, and Declan F. McCole. "Protein Tyrosine Phosphatase non-Receptor Type 2 regulates IFN-γ-induced cytokine signaling in THP-1 monocytes." Inflammatory Bowel Diseases 16, no. 12 (December 2010): 2055–64. http://dx.doi.org/10.1002/ibd.21325.

Full text

APA, Harvard, Vancouver, ISO, and other styles

48

HEINRICH, Peter C., Iris BEHRMANN, Serge HAAN, Heike M. HERMANNS, Gerhard MÜLLER-NEWEN, and Fred SCHAPER. "Principles of interleukin (IL)-6-type cytokine signalling and its regulation." Biochemical Journal 374, no. 1 (August 15, 2003): 1–20. http://dx.doi.org/10.1042/bj20030407.

Full text

Abstract:

The IL (interleukin)-6-type cytokines IL-6, IL-11, LIF (leukaemia inhibitory factor), OSM (oncostatin M), ciliary neurotrophic factor, cardiotrophin-1 and cardiotrophin-like cytokine are an important family of mediators involved in the regulation of the acute-phase response to injury and infection. Besides their functions in inflammation and the immune response, these cytokines play also a crucial role in haematopoiesis, liver and neuronal regeneration, embryonal development and fertility. Dysregulation of IL-6-type cytokine signalling contributes to the onset and maintenance of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, osteoporosis, multiple sclerosis and various types of cancer (e.g. multiple myeloma and prostate cancer). IL-6-type cytokines exert their action via the signal transducers gp (glycoprotein) 130, LIF receptor and OSM receptor leading to the activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) cascades. This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction. Emphasis is put on the termination and modulation of the JAK/STAT signalling pathway mediated by tyrosine phosphatases, the SOCS (suppressor of cytokine signalling) feedback inhibitors and PIAS (protein inhibitor of activated STAT) proteins. Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed.

APA, Harvard, Vancouver, ISO, and other styles

49

Prezioso, Giovanni, Laura Comegna, Concetta Di Giulio, Simone Franchini, Francesco Chiarelli, and Annalisa Blasetti. "C1858T Polymorphism of Protein Tyrosine Phosphatase Non-receptor Type 22 (PTPN22): an eligible target for prevention of type 1 diabetes?" Expert Review of Clinical Immunology 13, no. 3 (December 8, 2016): 189–96. http://dx.doi.org/10.1080/1744666x.2017.1266257.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

Cao, Xun, Yan-Zhen Chen, Ruo-Zhen Luo, Lin Zhang, Song-Liang Zhang, Jun Zeng, Yu-Chuan Jiang, Yu-Jing Han, and Zhe-Sheng Wen. "Tyrosine-protein phosphatase non-receptor type 12 expression is a good prognostic factor in resectable non-small cell lung cancer." Oncotarget 6, no. 13 (March 14, 2015): 11704–13. http://dx.doi.org/10.18632/oncotarget.3588.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Tyrosine protein phosphatase non-receptor type 11'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles