Physical and functional interactions between protein tyrosine phosphatase α, PI 3-kinase, and PKCδ

A. Steták, P. Csermely, A. Ullrich, G. Kéri

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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, PKCΔ and the protein tyrosine phosphatase α (PTPα). We show a physical interaction of PI 3-kinase and PKCΔ with PTPα and show that the tyrosine phosphatase plays a role in the activation of MAPK. In this process, PTPα Ser-180 and Ser-204 phosphorylation is critical for the induction of phosphatase activity, which is required for dephosphorylation of pp60c-src. Taken together, we demonstrate the physical and functional association between PI 3-kinase, PKCΔ and PTPα in a signaling complex that mediates the antitumor activity of the somatostatin analogue TT-232.

Original languageEnglish
Pages (from-to)564-572
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume288
Issue number3
DOIs
Publication statusPublished - Nov 2 2001

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Protein Tyrosine Phosphatases
Phosphatidylinositol 3-Kinases
Chemical activation
Somatostatin
Phosphoric Monoester Hydrolases
Cells
Phosphorylation
Cell proliferation
Cell Cycle Checkpoints
Tyrosine
Tumors
Cell Proliferation
Association reactions
Apoptosis
TT2-32
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Physical and functional interactions between protein tyrosine phosphatase α, PI 3-kinase, and PKCδ. / Steták, A.; Csermely, P.; Ullrich, A.; Kéri, G.

In: Biochemical and Biophysical Research Communications, Vol. 288, No. 3, 02.11.2001, p. 564-572.

Research output: Contribution to journalArticle

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