Phosphorylation of focal adhesion kinase at tyrosine 861 is crucial for ras transformation of fibroblasts

Yangmi Lim, Innoc Han, Jihyun Jeon, Haein Park, Young Yil Bahk, Eok Soo Oh

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Although elevated expression and increased tyrosine phosphorylation of focal adhesion kinase (FAK) are crucial for tumor progression, the mechanism by which FAK promotes oncogenic transformation is unclear. We have therefore determined the role of FAK phosphorylation at tyrosine 861 in the oncogenic transformation of NIH3T3 fibroblasts. FAK phosphorylation at tyrosine 861 was increased in both constitutively H-Ras-transformed and H-Ras-inducible NIH3T3 cells, in parallel with cell transformation. However, H-Ras-inducible cells transfected with the nonphosphorylatable mutant FAK Y861F showed decreased migration/invasion, focus forming activity and anchorage-independent growth, compared with either wild-type or kinase-defective FAK. In contrast to unaltered FAK/Src activity, the association of FAK and p130CAS was decreased in FAK Y861F-transfected cells, and FAK phosphorylation at tyrosine 861 enhanced this association in vitro. Consistently, FAK Y861F-transfected cells were defective in activation of c-Jun NH2-terminal kinase and in expression of matrix metalloproteinase-9 during transformation. Taken together, these results strongly suggest that FAK phosphorylation at tyrosine 861 is crucial for H-Ras-induced transformation through regulation of the association of FAK with p130CAS.

Original languageEnglish
Pages (from-to)29060-29065
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number28
DOIs
StatePublished - 9 Jul 2004

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