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PTP2C, an SH2 domain-containing protein-tyrosine phosphatase, is
recruited to the growth factor receptors upon stimulation of cells. To
investigate its role in growth factor signaling, we have overexpressed
by approximately 6-fold the native PTP2C and a catalytically inactive
mutant of the enzyme in 293 human embryonic kidney cells. The native
PTP2C was located entirely in the cytosol, while the inactive mutant
was nearly equally distributed in cytosolic and membrane fractions.
Expression of the latter caused hyperphosphorylation on tyrosine of a
43-kDa protein, which was co-immunoprecipitated and co-partitioned in
the plasma membrane fraction with the inactive PTP2C mutant. This
protein may represent a physiological substrate of PTP2C.
Overexpression of the native PTP2C enhanced epidermal growth factor
(EGF)-stimulated mitogen-activated protein (MAP) kinase kinase activity
by 30%, whereas expression of the inactive mutant reduced the
stimulated activity by 50%. Similar effects were observed for the
activation of MAP kinase as determined by activity assay, gel mobility
shift, and tyrosine phosphorylation. The data suggest that the
phosphatase activity of PTP2C is partly required for MAP kinase
activation by EGF and that PTP2C may function by dephosphorylating the
43-kDa membrane protein.
Volume 270,
Number 20,
Issue of May 19, pp. 11765-11769, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
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L. Su, Z. Zhao, P. Bouchard, D. Banville, E. H. Fischer, E. G. Krebs, and S.-H. Shen Positive Effect of Overexpressed Protein-tyrosine Phosphatase PTP1C on Mitogen-activated Signaling in 293 Cells J. Biol. Chem., April 26, 1996; 271(17): 10385 - 10390. [Abstract] [Full Text] [PDF]
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L. Guillemot, A. Levy, Z. J. Zhao, G. Bereziat, and B. Rothhut The Protein-tyrosine Phosphatase SHP-2 Is Required during Angiotensin II-mediated Activation of Cyclin D1 Promoter in CHO-AT1A Cells J. Biol. Chem., August 18, 2000; 275(34): 26349 - 26358. [Abstract] [Full Text] [PDF]
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M. Machide, K. Kamitori, and S. Kohsaka Hepatocyte Growth Factor-induced Differential Activation of Phospholipase Cgamma 1 and Phosphatidylinositol 3-Kinase Is Regulated by Tyrosine Phosphatase SHP-1 in Astrocytes J. Biol. Chem., September 29, 2000; 275(40): 31392 - 31398. [Abstract] [Full Text] [PDF]
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F. Xu, R. Zhao, Y. Peng, A. Guerrah, and Z. J. Zhao Association of Tyrosine Phosphatase SHP-2 with F-actin at Low Cell Densities J. Biol. Chem., July 27, 2001; 276(31): 29479 - 29484. [Abstract] [Full Text] [PDF]
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