Regulation of fibroblast motility by the protein tyrosine phosphatase PTP-PEST

Garton, A. J., Tonks, N. K. (February 1999) Regulation of fibroblast motility by the protein tyrosine phosphatase PTP-PEST. Journal of Biological Chemistry, 274 (6). pp. 3811-3818. ISSN 0021-9258

Abstract

The protein tyrosine phosphatase PTP-PEST is a cytosolic enzyme that displays a remarkable degree of selectivity for tyrosine-phosphorylated p130(Cas) as a substrate, both in vitro and in intact cells, We have investigated the physiological role of PTP-PEST using Rat1 fibroblast-derived stable cell lines that we have engineered to overexpress PTP-PEST. These cell lines exhibit normal levels of tyrosine phosphorylation of the majority of proteins but have significantly lower levels of tyrosine phosphorylation of p130(Cas) than control cells. Initial cellular events occurring following integrin-mediated attachment to fibronectin (cell attachment and spreading) are essentially unchanged in cells overexpressing PTP-PEST; similarly, the extent and time course of mitogen-activated protein kinase activation in response to integrin engagement is unchanged. In contrast, the reduced phosphorylation state of p130(Cas) is associated with a considerably reduced rate of cell migration and a failure of cells overexpressing PTP-PEST to accomplish the normally observed redistribution of p130(Cas) to the leading edge of migrating cells. Furthermore, cells overexpressing PTP-PEST demonstrate significantly reduced levels of association of p130(Cas) with the Crk adaptor protein. Our results suggest that one physiological role of PTP-PEST is to dephosphorylate p130(Cas), thereby controlling tyrosine phosphorylation dependent signaling events downstream of p130(Cas) and regulating cell migration.

Item Type: Paper
Uncontrolled Keywords: FOCAL ADHESION KINASE MEDIATED CELL-ADHESION SWISS 3T3 CELLS PHOSPHOTYROSINE-CONTAINING PROTEINS V-CRK ONCOGENE GROWTH-FACTOR SUBSTRATE P130(CAS) SH3 DOMAINS SRC KINASE C-SRC
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell motility
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > protein tyrosine phosphatase
CSHL Authors:
Communities: CSHL labs > Tonks lab
Depositing User: Matt Covey
Date: February 1999
Date Deposited: 18 Dec 2013 17:08
Last Modified: 18 Dec 2013 17:08
Related URLs:
URI: https://repository.cshl.edu/id/eprint/29027

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