Functional interaction between SHPTP1 and the Lyn tyrosine kinase in the apoptotic response to DNA damage.
The Lyn protein-tyrosine kinase is activated in the cellular response to DNA-damaging agents. Here we demonstrate that Lyn associates constitutively with the SHPTP1 protein-tyrosine phosphatase. The SH3 domain of Lyn interacts directly with SHPTP1. The results show that Lyn phosphorylates SHPTP1 at the C-terminal Tyr-564 site. Lyn-mediated phosphorylation of SHPTP1 ... stimulates SHPTP1 tyrosine phosphatase activity. We also demonstrate that treatment of cells with 1-beta-D-arabinofuranosylcytosine and other genotoxic agents induces Lyn-dependent phosphorylation and activation of SHPTP1. The significance of the Lyn-SHPTP1 interaction is supported by the demonstration that activation of Lyn contributes in part to the apoptotic response to ara-C treatment and that SHPTP1 attenuates this response. These findings support a functional interaction between Lyn and SHPTP1 in the response to DNA damage.
Mesh Terms:
Apoptosis, Cell Cycle, Cytarabine, DNA Damage, Down-Regulation, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Phosphorylation, Precipitin Tests, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Recombinant Fusion Proteins, Time Factors, Transfection, U937 Cells, src-Family Kinases
Apoptosis, Cell Cycle, Cytarabine, DNA Damage, Down-Regulation, Hela Cells, Humans, Intracellular Signaling Peptides and Proteins, Phosphorylation, Precipitin Tests, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Recombinant Fusion Proteins, Time Factors, Transfection, U937 Cells, src-Family Kinases
J. Biol. Chem.
Date: Dec. 03, 1999
PubMed ID: 10574931
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