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Cell transformation and activation of pp60c-src by overexpression of a protein tyrosine phosphatase

Abstract

THE kinase activity of pp60c-src is specifically and transiently increased during mitosis and repressed during interphase1. Loss of cell-cycle control of pp60c-src occurs on mutation of Tyr 527 to Phe or when pp60c-src is associated with polyoma middle-T-antigen, and these conditions result in cell transformation or tumorigenesis2,3. In both cases, pp60c-src has elevated kinase activity which is maintained throughout the cell cycle and accom-panied by dephosphorylation of the carboxy-terminal negative regulatory4–7 Tyr 527 site, or mimicry of Tyr 527 dephosphoryla-tion in the case of the mutant. Here we report that overexpression of the receptor-like protein tyrosine phosphatase PTPα8–10 results in persistent activation of pp60c-src kinase, with concomitant cell transformation and tumorigenesis. In PTPα-overexpressing cells, the pp60c-src kinase activation is accompanied by dephosphorylation at Tyr 527, and direct dephosphorylation of this site by purified PTPα occurs in vitro. Our results suggest that PTPα is involved in the regulation of cell proliferation, exerting at least some of its effects through pp60c-src kinase, and has oncogenic capability when overexpressed.

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Zheng, X., Wang, Y. & Fallen, C. Cell transformation and activation of pp60c-src by overexpression of a protein tyrosine phosphatase. Nature 359, 336–339 (1992). https://doi.org/10.1038/359336a0

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