Abstract
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 cytsolic and membrane fractions. Expression of the latter caused hyperphosphorylation on tyrosine of a 43-kDa protein, which was coimmunoprecipitated 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 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.
Highlights
External signals, such as growth factors, initiate their signals by binding to ligand-specific growth factor receptors on the cellular membrane [1]
We found that overexpression of PTP2C slightly increased epidermal growth factor (EGF)-induced activation of mitogen-activated protein (MAP) kinase while overexpression of the catalytically inactive mutant of PTP2C modestly decreased such activation
The data suggest that the phosphatase activity of PTP2C is at least partly required for MAP kinase activation
Summary
Vol 270, No 20, Issue of May 19, pp. 11765-11769, 1995 Printed in U.S.A. Altered Expression of Protein-tyrosine Phosphatase 2C in 293 Cells Affects Protein Tyrosine Phosphorylation and Mitogen-activated Protein Kinase Activation*. 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 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 External signals, such as growth factors, initiate their signals by binding to ligand-specific growth factor receptors on the cellular membrane [1]. To investigate the role of PTP2C in growth factor signaling, we have expressed the native PTP2C and a catalytic inactive form of the enzyme in 293 human embryonic kidney cells.
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