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

Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):6898-901. doi: 10.1073/pnas.93.14.6898.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases / biosynthesis
  • Calcium-Calmodulin-Dependent Protein Kinases / radiation effects
  • Cell Line
  • Cesium Radioisotopes
  • DNA Damage*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • JNK Mitogen-Activated Protein Kinases
  • Leukemia, Myeloid
  • Mice
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / isolation & purification
  • Protein Tyrosine Phosphatases / metabolism*
  • Protein Tyrosine Phosphatases / radiation effects*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Proto-Oncogene Proteins c-abl / radiation effects
  • Radiation, Ionizing
  • Recombinant Proteins / metabolism
  • Stress, Physiological
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Cesium Radioisotopes
  • Intracellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-abl
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse
  • Ptpn6 protein, mouse