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

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 417-326) in the catalytic domain of SHPTP1 and that c-Abl phosphorylates C terminal Y536 and YJ64 sites. The functional significance of the c-Abl-SHPTP1 interaction is supported hy the demonstration that, like c-Abl, SGPTP1 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.