The stress response to ionizing radiation involoves 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 417-426) 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.
Mesh Terms:
3T3 Cells, Amino Acid Sequence, Animals, Binding Sites, Calcium-Calmodulin-Dependent Protein Kinases, 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, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-abl, Radiation, Ionizing, Recombinant Proteins, Stress, Physiological, Transfection, Tumor Cells, Cultured
3T3 Cells, Amino Acid Sequence, Animals, Binding Sites, Calcium-Calmodulin-Dependent Protein Kinases, 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, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-abl, Radiation, Ionizing, Recombinant Proteins, Stress, Physiological, Transfection, Tumor Cells, Cultured
Proc. Natl. Acad. Sci. U.S.A.
Date: Jul. 09, 1996
PubMed ID: 8692915
View in: Pubmed Google Scholar
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