Vascular Endothelial Growth Factor Induces the Disorganization of Actin Stress Fibers Accompanied by Protein Tyrosine Phosphorylation and Morphological Change in BALB/C3T3 Cells

1994 ◽  
Vol 202 (3) ◽  
pp. 1716-1723 ◽  
Author(s):  
T. Enomoto ◽  
T. Okamoto ◽  
J.D. Sato
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Morphological Change ◽  
Tyrosine Phosphorylation ◽  
Stress Fibers ◽  
Vascular Endothelial ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Endothelial Growth Factor ◽  
Actin Stress Fibers

scholarly journals Tyrosine phosphatase PTP-MEG2 negatively regulates vascular endothelial growth factor receptor signaling and function in endothelial cells

2012 ◽  
Vol 303 (5) ◽  
pp. C548-C553 ◽  
Author(s):  
Qin Hao ◽  
Buka Samten ◽  
Hong-Long Ji ◽  
Z. Joe Zhao ◽  
Hua Tang
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Vascular Endothelial ◽  
Wild Type ◽  
Protein Tyrosine ◽  
Vegfr2 Signaling ◽  
And Function ◽  
Endothelial Growth Factor

Protein tyrosine phosphorylation is a fundamental mechanism for diverse physiological processes, which is regulated by protein tyrosine kinases and protein tyrosine phosphatases (PTPs). In this study, we searched for protein substrates of PTP-MEG2 (also called PTPN9), a nonreceptor PTP, and investigated its function in endothelial cells (ECs). By using a PTP-MEG2 substrate-trapping DA mutant, we found that a couple of tyrosine-phosphorylated proteins were associated with the DA mutant but not wild-type PTP-MEG2 and that the association was enhanced by vascular endothelial growth factor (VEGF) in ECs. We further found that VEGF receptor 2 (VEGFR2) was coimmunopricipitated with the DA mutant but not wild-type PTP-MEG2. The VEGF-induced phosphorylation of VEGFR2 on Tyr1175, a critical autophosphorylation site for VEGFR2 signaling, was inhibited 70% by overexpression of wild-type PTP-MEG2 but was enhanced (2.2-fold) by the DA mutant of PTP-MEG2. We also found that PTP-MEG2 DA mutant preferentially associated with Janus kinase 1 (JAK1) but not with other JAK kinases (Tyk2 and JAK2) present in ECs and regulated JAK1 tyrosine phosphorylation. Lastly, the VEGF-induced signal transduction and the production of interleukin (IL)-6 were significantly enhanced by PTP-MEG2 knockdown in ECs, whereas the VEGF-induced IL-6 production was inhibited 50% by PTP-MEG2 overexpression. Thus we have indentified VEGFR2 as a PTP-MEG2 substrate, and our findings indicate that PTP-MEG2 is a negative regulator of VEGFR2 signaling and function in ECs.

scholarly journals The type 2 vascular endothelial growth factor receptor recruits insulin receptor substrate-1 in its signalling pathway

2002 ◽  
Vol 368 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Duraisamy SENTHIL ◽  
Goutam GHOSH CHOUDHURY ◽  
Basant K. BHANDARI ◽  
Balakuntalam S. KASINATH
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Protein Synthesis ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Tyrosine Phosphorylation ◽  
Kinase Activity ◽  
Insulin Receptor Substrate ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) isoforms exert their biological effects through receptors that possess intrinsic tyrosine kinase activity. Whether VEGF binding to its receptors recruits insulin receptor substrate (IRS) family of docking proteins to the receptor is not known. Following incubation of mouse kidney proximal tubular epithelial cells with VEGF, we observed an increase in tyrosine phosphorylation of several proteins, including one of 200kDa, suggesting possible regulation of phosphorylation of IRS proteins. VEGF augmented tyrosine phosphorylation of IRS-1 in kidney epithelial cells and rat heart endothelial cells in a time-dependent manner. In the epithelial cells, association of IRS-1 with type 2 VEGF receptor was promoted by VEGF. VEGF also increased association of IRS-1 with the p85 regulatory subunit of phosphoinositide 3-kinase (PI 3-kinase), and PI 3-kinase activity in IRS-1 immunoprecipitates was increased in VEGF-treated cells. Incubation of epithelial cells with antisense IRS-1 oligonucleotide, but not sense oligonucleotide, reduced expression of the protein and VEGF-induced PI 3-kinase activity in IRS-1 immunoprecipitates. Additionally, VEGF-induced protein synthesis was also impaired by antisense but not sense IRS-1 oligonucleotide. These data provide the first evidence that binding of VEGF to its type 2 receptor promotes association of IRS-1 with the receptor complex. This association may account for some of the increase in VEGF-induced PI 3-kinase activity, and the increase in de novo protein synthesis seen in renal epithelial cells.

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