CELL CYCLE PTP Regulates Src During Mitosis

Abstract: Protein tyrosine phosphatase (PTP) can stimulate the activity of Src-family kinases. The activation process involves modification of an intramolecular interaction on Src, whereby the Src homology 2 (SH2) domain, which is bound to an inhibitory phosphotyrosine located at the COOH-terminus of Src, becomes bound instead to a phosphotyrosine moiety on PTP. This exposes the Src inhibitory phosphotyrosine, allowing PTP to dephosphorylate it, which leads to Src activation. Zheng and Shalloway have found that PTP is activated during mitosis, before Src activation is observed. Inactive tyrosine phosphorylated PTP is bound by the Grb2 adapter protein, at the site on PTP required for SH2 domain displacement. The authors found that increased phosphorylation on serine residues in PTP led to reduced association of Grb2 with PTP during mitosis, which correlated with the activation of Src. Additionally, during mitosis in PTP^–/– cells, Src was not activated, indicating that PTP has an important physiological role in regulating the activity of Src.

X.-M. Zheng, D. Shalloway, Two mechanisms activate PTP during mitosis. EMBO J. 20, 6037-6049 (2001). [Abstract] [Full Text]