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. 1996 Jul 9;93(14):6898–6901. doi: 10.1073/pnas.93.14.6898

The stress response to ionizing radiation involoves c-Abl-dependent phosphorylation of SHPTP1.

S Kharbanda 1, A Bharti 1, D Pei 1, J Wang 1, P Pandey 1, R Ren 1, R Weichselbaum 1, C T Walsh 1, D Kufe 1
PMCID: PMC38905  PMID: 8692915

Abstract

c-Abl is a nonreceptor tyrosine kinase that is activated by certain DNA-damaging agents. The present studies demonstrate that nuclear c-Abl binds constitutively to the protein tyrosine phosphatase SHPTP1. Treatment with ionizing radiation is associated with c-Abl-dependent tyrosine phosphorylation of SHPTP1. The results demonstrate that the SH3 domain of c-Abl interacts with a WPDHGVPSEP motif (residues 417-426) in the catalytic domain of SHPTP1 and that c-Abl phosphorylates C terminal Y536 and Y564 sites. The functional significance of the c-Abl-SHPTP1 interaction is supported by the demonstration that, like c-Abl, SHPTP1 regulates the induction of Jun kinase activity following DNA damage. These findings indicate that SHPTP1 is involved in the response to genotoxic stress through a c-Abl-dependent mechanism.

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Selected References

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