¹Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China

²Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan, Republic of China

Correspondence to: T-H Leu, E-mail: tzengleu@mail.ncku.edu.tw

Tyr-397 phosphorylation is important for focal adhesion kinase (FAK)-mediated signalling. In vitro FAK immunocomplex kinase experiments demonstrated that both FAK Tyr-576/577 and Tyr-863 phosphorylation regulated FAK Tyr-397 phosphorylation. While the former increased the intermolecular transphosphorylation activity of FAK, the latter was crucial for its cis-phosphorylation. This observation was further supported by the reduced complex formation between Src and 3F-FAK (576F/577F/863F-FAK) as compared to that between Src and 576F/577F-FAK or Src and 863F-FAK. Regulation of cis- and transphosphorylation activities of FAK by such a differential tyrosyl phosphorylation mechanism is unprecedented. Furthermore, in fibronectin-stimulated cells, both Tyr-576/577 and Tyr-863 phosphorylation could enhance FAK Tyr-397 phosphorylation. This observation implies that integrin-mediated FAK Tyr-397 phosphorylation was also regulated through both FAK cis- and transphosphorylation mechanisms.

Oncogene (2002) 21, 6992-7000. doi:10.1038/sj.onc.1205904

Src; FAK; tyrosine kinase; tyrosol phosphorylation