| http://purl.uniprot.org/citations/12937170 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12937170 | http://www.w3.org/2000/01/rdf-schema#comment | "DNA damage induced by radiation or DNA-damaging agents leads to apoptosis and cell cycle arrest. However, DNA damage-triggered signal transduction involved in these cellular responses is not well understood. We previously demonstrated an important role for SHP-2, a ubiquitously expressed SH2 domain-containing tyrosine phosphatase, in the DNA damage-induced apoptotic response. Here we report a potential role for SHP-2 in a DNA damage-activated cell cycle checkpoint. Cell cycle analysis and the mitotic index assay showed that following DNA damage induced by cisplatin or gamma-irradiation, the G2 (but not S) arrest response was diminished in SV40 large T antigen-immortalized embryonic fibroblast cells lacking functional SHP-2. Notably, reintroduction of wild-type SHP-2 into the mutant cells fully restored the DNA damage-induced G2 arrest response, suggesting a direct role of SHP-2 in the G2/M checkpoint. Further biochemical analysis revealed that SHP-2 constitutively associated with 14-3-3beta, and that Cdc25C cytoplasmic translocation induced by DNA damage was essentially blocked in SHP-2 mutant cells. Additionally, we showed that following DNA damage, activation of p38 kinase was significantly elevated, while Erk kinase activation was decreased in mutant cells, and treatment of SHP-2 mutant cells with SB203580, a selective inhibitor for p38 kinase, partially restored the DNA damage-induced G2 arrest response. These results together provide the first evidence that SHP-2 tyrosine phosphatase enhances the DNA damage G2/M checkpoint in SV40 large T antigen immortalized murine embryonic fibroblast cells."xsd:string |
| http://purl.uniprot.org/citations/12937170 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m305075200"xsd:string |
| http://purl.uniprot.org/citations/12937170 | http://purl.uniprot.org/core/author | "Yuan L."xsd:string |
| http://purl.uniprot.org/citations/12937170 | http://purl.uniprot.org/core/author | "Qu C.K."xsd:string |
| http://purl.uniprot.org/citations/12937170 | http://purl.uniprot.org/core/author | "Yu W.M."xsd:string |
| http://purl.uniprot.org/citations/12937170 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12937170 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/12937170 | http://purl.uniprot.org/core/pages | "42812-42820"xsd:string |
| http://purl.uniprot.org/citations/12937170 | http://purl.uniprot.org/core/title | "DNA damage-induced G2/M checkpoint in SV40 large T antigen-immortalized embryonic fibroblast cells requires SHP-2 tyrosine phosphatase."xsd:string |
| http://purl.uniprot.org/citations/12937170 | http://purl.uniprot.org/core/volume | "278"xsd:string |
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