title: A cross-talk between oncogenic Ras and tumor suppressor PTEN through FAK Tyr861 phosphorylation in NIH/3T3 mouse embryonic fibroblasts.
abstract: Although Ras is a potent oncogene, its tumorigenicity depends on cellular context and cooperative events. Tumor suppressor PTEN is the most important negative regulator of the cell-survival signaling pathway initiated by phosphoinositide 3-OH kinase. Previously, we established various NIH/3T3 cells expressing H-Ras mutant proteins. This report shows that expression of PTEN is suppressed by the oncogenic H-Ras at its protein and transcript levels as well as by oncogenic K- and N-Ras. This activity of oncogenic Ras is mediated by Raf-1/Erk/MEK signaling pathway. In our previous reports, FAK Y(861) phosphorylation is higher in H-Ras transformed NIH/3T3 cells. In this report, level of FAK pY(861) was examined in Ras mutant cell lines. By generating wild-type PTEN, lipid phosphatase-deficient PTEN and activity-inert PTEN-inducible cell lines in the background of oncogenic H-Ras stable expression in NIH/3T3 cells, we show level of FAK pY(861) is decreased by protein phosphatase activity of PTEN.
authors.affiliation: Protein Network Research Center, Yonsei University, 134, Shinchon-Dong, Seodeamoon-Gu, Seoul 120-749, Republic of Korea. bahk12@empal.com
authors.forename: Young Yil
authors.initials: YY
authors.lastname: Bahk
authors.forename: Ick-Hyun
authors.initials: IH
authors.lastname: Cho
authors.forename: Tong Soo
authors.initials: TS
authors.lastname: Kim
mesh_terms: D000818:Animals; D005347:Fibroblasts; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014443:Tyrosine; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D018631:ras Proteins