scholarly journals Cover Picture: Selective Inhibitors of the Protein Tyrosine Phosphatase SHP2 Block Cellular Motility and Growth of Cancer Cells in vitro and in vivo (ChemMedChem 5/2015)

ChemMedChem ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. 757-757
Author(s):  
Stefanie Grosskopf ◽  
Chris Eckert ◽  
Christoph Arkona ◽  
Silke Radetzki ◽  
Kerstin Böhm ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Cellular Motility ◽  
Selective Inhibitors ◽  
Protein Tyrosine

Selective Inhibitors of the Protein Tyrosine Phosphatase SHP2 Block Cellular Motility and Growth of Cancer Cells in vitro and in vivo

ChemMedChem ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. 815-826 ◽  
Author(s):  
Stefanie Grosskopf ◽  
Chris Eckert ◽  
Christoph Arkona ◽  
Silke Radetzki ◽  
Kerstin Böhm ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Cellular Motility ◽  
Selective Inhibitors ◽  
Protein Tyrosine

Protein-tyrosine phosphatase activity of CD45 is activated by sequential phosphorylation by two kinases

1994 ◽  
Vol 14 (8) ◽  
pp. 5523-5532
Author(s):  
D R Stover ◽  
K A Walsh
Keyword(s):  
T Cell Activation ◽  
Protein Tyrosine Phosphatase ◽  
Time Course ◽  
Cell Activation ◽  
Regulatory Mechanism ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine

We describe a potential regulatory mechanism for the transmembrane protein-tyrosine phosphatase CD45. Phosphorylation on both tyrosine and serine residues in vitro results in an activation of CD45 specifically toward one artificial substrate but not another. The activation of these kinases appears to be order dependent, as it is enhanced when phosphorylation of tyrosine precedes that of serine but phosphorylation in the reverse order yields no activation. Any of four protein-tyrosine kinases tested, in combination with the protein-serine/threonine kinase, casein kinase II, was capable of mediating this activation in vitro. The time course of phosphorylation of CD45 in response to T-cell activation is consistent with the possibility that this regulatory mechanism is utilized in vivo.

Lithium regulates protein tyrosine phosphatase activity in vitro and in vivo

2002 ◽  
Vol 162 (4) ◽  
pp. 379-384 ◽  
Author(s):  
Xuechu Zhen ◽  
Claudio Torres ◽  
Eitan Friedman
Keyword(s):  
Phosphatase Activity ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine

scholarly journals Identification of a Nuclear Stat1 Protein Tyrosine Phosphatase

2002 ◽  
Vol 22 (16) ◽  
pp. 5662-5668 ◽  
Author(s):  
Johanna ten Hoeve ◽  
Maria de Jesus Ibarra-Sanchez ◽  
Yubin Fu ◽  
Wei Zhu ◽  
Michel Tremblay ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Nuclear Extract ◽  
Null Mouse ◽  
Protein Tyrosine ◽  
Nuclear Extracts ◽  
Unknown Protein ◽  
Stat1 Protein

ABSTRACT Upon interferon (IFN) stimulation, Stat1 becomes tyrosine phosphorylated and translocates into the nucleus, where it binds to DNA to activate transcription. The activity of Stat1 is dependent on tyrosine phosphorylation, and its inactivation in the nucleus is accomplished by a previously unknown protein tyrosine phosphatase (PTP). We have now purified a Stat1 PTP activity from HeLa cell nuclear extract and identified it as TC45, the nuclear isoform of the T-cell PTP (TC-PTP). TC45 can dephosphorylate Stat1 both in vitro and in vivo. Nuclear extracts lacking TC45 fail to dephosphorylate Stat1. Furthermore, the dephosphorylation of IFN-induced tyrosine-phosphorylated Stat1 is defective in TC-PTP-null mouse embryonic fibroblasts (MEFs) and primary thymocytes. Reconstitution of TC-PTP-null MEFs with TC45, but not the endoplasmic reticulum (ER)-associated isoform TC48, rescues the defect in Stat1 dephosphorylation. The dephosphorylation of Stat3, but not Stat5 or Stat6, is also affected in TC-PTP-null cells. Our results identify TC45 as a PTP responsible for the dephosphorylation of Stat1 in the nucleus.

scholarly journals Involvement of the Mitochondrial Protein Tyrosine Phosphatase PTPM1 in the Promotion of Conidiation, Development, and Pathogenicity in Colletotrichum graminicola

2021 ◽  
Vol 11 ◽  
Author(s):  
Shaowei Wang ◽  
Guihua Li ◽  
Yi Wei ◽  
Gang Wang ◽  
Yuejia Dang ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Fungal Pathogens ◽  
Tyrosine Phosphatase ◽  
Mitochondrial Protein ◽  
Protein Tyrosine Phosphatases ◽  
Host Cells ◽  
Colletotrichum Graminicola ◽  
Protein Tyrosine

The phosphorylation status of proteins, which is determined by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), governs many cellular actions. In fungal pathogens, phosphorylation-mediated signal transduction has been considered to be one of the most important mechanisms in pathogenicity. Colletotrichum graminicola is an economically important corn pathogen. However, whether phosphorylation is involved in its pathogenicity is unknown. A mitochondrial protein tyrosine phosphatase gene, designated CgPTPM1, was deduced in C. graminicola through the use of bioinformatics and confirmed by enzyme activity assays and observation of its subcellular localization. We then created a CgPTPM1 deletion mutant (ΔCgPTPM1) to analyze its biological function. The results indicated that the loss of CgPTPM1 dramatically affected the formation of conidia and the development and differentiation into appressoria. However, the colony growth and conidial morphology of the ΔCgPTPM1 strains were unaffected. Importantly, the ΔCgPTPM1 mutant strains exhibited an obvious reduction of virulence, and the delayed infected hyphae failed to expand in the host cells. In comparison with the wild-type, ΔCgPTPM1 accumulated a larger amount of H2O2 and was sensitive to exogenous H2O2. Interestingly, the host cells infected by the mutant also exhibited an increased accumulation of H2O2 around the infection sites. Since the expression of the CgHYR1, CgGST1, CgGLR1, CgGSH1 and CgPAP1 genes was upregulated with the H2O2 treatment, our results suggest that the mitochondrial protein tyrosine phosphatase PTPM1 plays an essential role in promoting the pathogenicity of C. graminicola by regulating the excessive in vivo and in vitro production of H2O2.

scholarly journals Functions of the Ectodomain and Cytoplasmic Tyrosine Phosphatase Domains of Receptor Protein Tyrosine Phosphatase Dlar In Vivo

2003 ◽  
Vol 23 (19) ◽  
pp. 6909-6921 ◽  
Author(s):  
Neil X. Krueger ◽  
R. Sreekantha Reddy ◽  
Karl Johnson ◽  
Jack Bateman ◽  
Nancy Kaufmann ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
P Element ◽  
Receptor Protein ◽  
Loss Of Function ◽  
Protein Tyrosine ◽  
Receptor Protein Tyrosine Phosphatase ◽  
Catalytically Active

ABSTRACT The receptor protein tyrosine phosphatase (PTPase) Dlar has an ectodomain consisting of three immunoglobulin (Ig)-like domains and nine fibronectin type III (FnIII) repeats and a cytoplasmic domain consisting of two PTPase domains, membrane-proximal PTP-D1 and C-terminal PTP-D2. A series of mutant Dlar transgenes were introduced into the Drosophila genome via P-element transformation and were then assayed for their capacity to rescue phenotypes caused by homozygous loss-of-function genotypes. The Ig-like domains, but not the FnIII domains, are essential for survival. Conversely, the FnIII domains, but not the Ig-like domains, are required during oogenesis, suggesting that different domains of the Dlar ectodomain are involved in distinct functions during Drosophila development. All detectable PTPase activity maps to PTP-D1 in vitro. The catalytically inactive mutants of Dlar were able to rescue Dlar −/− lethality nearly as efficiently as wild-type Dlar transgenes, while this ability was impaired in the PTP-D2 deletion mutants DlarΔPTP-D2 and Dlarbypass . Dlar-C1929S, in which PTP-D2 has been inactivated, increases the frequency of bypass phenotype observed in Dlar −/− genotypes, but only if PTP-D1 is catalytically active in the transgene. These results indicate multiple roles for PTP-D2, perhaps by acting as a docking domain for downstream elements and as a regulator of PTP-D1.

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