SHP-2 phosphatase activity is required for PECAM-1-dependent cell motility.

American Journal of Physiology. Cell Physiology
Jing-Xu ZhuHorace M DeLisser

Abstract

Platelet endothelial cell adhesion molecule-1 (PECAM-1) has been implicated in endothelial cell motility during angiogenesis. Although there is evidence that SHP-2 plays a role in PECAM-1-dependent cell motility, the molecular basis of the activity of SHP-2 in this process has not been defined. To investigate the requirement of SHP-2 in PECAM-1-dependent cell motility, studies were done in which various constructs of SHP-2 were expressed in cell transfectants expressing PECAM-1. We observed that the levels of PECAM-1 tyrosine phosphorylation and SHP-2 association with PECAM-1 were significantly increased in cells expressing a phosphatase-inactive SHP-2 mutant, suggesting that the level of PECAM-1 tyrosine phosphorylation, and thus SHP-2 binding are regulated in part by bound, catalytically active SHP-2. We subsequently found that expression of PECAM-1 stimulated wound-induced migration and the formation of filopodia (a morphological feature of motile cells). These activities were associated with increased mitogen-activated protein kinase (MAPK) activation and the dephosphorylation of paxillin (an event implicated in the activation of MAPK). The phosphatase-inactive SHP-2 mutant, however, suppressed these PECAM-1-dependent pheno...Continue Reading

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Citations

Jul 30, 2011·Journal of Signal Transduction·Xia Liu, Cheng-Kui Qu
Jan 18, 2014·Cell and Tissue Research·Jamie R Privratsky, Peter J Newman
Nov 30, 2016·Physiological Reports·Valsamma AbrahamHorace M DeLisser
Apr 8, 2016·Current Opinion in Hematology·Panida LertkiatmongkolPeter J Newman
Oct 12, 2010·Cell Adhesion & Migration·Horace M DeLisser
May 31, 2018·International Journal of Oncology·Valsamma AbrahamHorace M DeLisser

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