Physical and functional interactions between protein tyrosine phosphatase alpha, PI 3-kinase, and PKCdelta.

The somatostatin analogue, TT-232 inhibits cell proliferation and induces apoptosis in a variety of tumor cells both in vivo and in vitro. While the early transient activation of Erk/MAPK was found to be important for the induction of cell cycle arrest, the signaling pathway leading to the activation of Erk/MAPK ...
had not been fully established. Here we present evidence that activation of the Erk/MAPK pathway by TT-232 involves PI 3-kinase, PKCdelta and the protein tyrosine phosphatase alpha (PTPalpha). We show a physical interaction of PI 3-kinase and PKCdelta with PTPalpha and show that the tyrosine phosphatase plays a role in the activation of MAPK. In this process, PTPalpha Ser-180 and Ser-204 phosphorylation is critical for the induction of phosphatase activity, which is required for dephosphorylation of pp60(c-src). Taken together, we demonstrate the physical and functional association between PI 3-kinase, PKCdelta and PTPalpha in a signaling complex that mediates the antitumor activity of the somatostatin analogue TT-232.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Animals, Antineoplastic Agents, COS Cells, Cells, Cultured, Enzyme Activation, GTP-Binding Proteins, Genes, src, Heterogeneous-Nuclear Ribonucleoprotein Group F-H, Humans, Isoenzymes, Mitogen-Activated Protein Kinases, Peptides, Cyclic, Phosphorylation, Protein Kinase C, Protein Kinase C-delta, Protein Tyrosine Phosphatases, RNA-Binding Proteins, Serine, Signal Transduction, Somatostatin, Virulence Factors, Bordetella
Biochem. Biophys. Res. Commun.
Date: Nov. 02, 2001
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