Identification and functional characterization of p130Cas as a substrate of protein tyrosine phosphatase nonreceptor 14

摘要: Protein tyrosine phosphatase nonreceptor type 14 (PTPN14) is frequently mutated in a variety of human cancers. However, the cell signaling pathways regulated by PTPN14 largely remain to be elucidated. Here, we identify list potential substrates using phospho-proteomic approach. We show that p130 Crk-associated substrate (p130Cas) direct and specifically regulates p130Cas phosphorylation at residue 128 (Y128) colorectal cancer (CRC) cells. engineered CRC cells homozygous for Y128F knock-in mutant found these exhibit significantly reduced migration colony formation, impaired anchorage-independent growth, slower xenograft tumor growth nude mice have decreased AKT. Furthermore, demonstrate SRC phosphorylates Y128 lines harboring high levels pY128Cas are more sensitive family kinase inhibitor Dasatinib. These findings suggest may exploited as predictive marker Dasatinib response patients. In aggregate, our studies reveal novel pathway has an important role tumorigenesis.