PMID- 10574931 OWN - NLM STAT- MEDLINE DCOM- 20000203 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 49 DP - 1999 Dec 3 TI - Functional interaction between SHPTP1 and the Lyn tyrosine kinase in the apoptotic response to DNA damage. PG - 34663-8 AB - 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. FAU - Yoshida, K AU - Yoshida K AD - Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Kharbanda, S AU - Kharbanda S FAU - Kufe, D AU - Kufe D LA - eng GR - CA29431/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 04079A1RDZ (Cytarabine) RN - EC 2.7.10.2 (lyn protein-tyrosine kinase) RN - EC 2.7.10.2 (src-Family Kinases) RN - EC 3.1.3.48 (PTPN11 protein, human) RN - EC 3.1.3.48 (PTPN6 protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) SB - IM MH - *Apoptosis MH - Cell Cycle MH - Cytarabine/pharmacology MH - *DNA Damage MH - Down-Regulation MH - HeLa Cells MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - Phosphorylation/drug effects MH - Precipitin Tests MH - Protein Tyrosine Phosphatase, Non-Receptor Type 11 MH - Protein Tyrosine Phosphatase, Non-Receptor Type 6 MH - Protein Tyrosine Phosphatases/*metabolism MH - Recombinant Fusion Proteins/metabolism MH - Time Factors MH - Transfection MH - U937 Cells MH - src-Family Kinases/*metabolism EDAT- 1999/11/27 00:00 MHDA- 1999/11/27 00:01 CRDT- 1999/11/27 00:00 PHST- 1999/11/27 00:00 [pubmed] PHST- 1999/11/27 00:01 [medline] PHST- 1999/11/27 00:00 [entrez] AID - 10.1074/jbc.274.49.34663 [doi] AID - S0021-9258(19)53374-9 [pii] PST - ppublish SO - J Biol Chem. 1999 Dec 3;274(49):34663-8. doi: 10.1074/jbc.274.49.34663.