Abstract
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.
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Acknowledgements
We would like to thank Drs Sarah J Parsons and J Thomas Parsons for providing us with the Src mAbs and cDNA constructs of fak and Src. We appreciate the technical help provided by Ruey-Wen Lin and Ya-Chun Chuang. This work was supported by National Science Council Grant (NSC 89-2311-B-040-009 to MC Maa), NHRI (NHRI-EX90-8932SL to TH Leu) and by MOE Program for Promoting Academic Excellence of Universities (91-B-FAO9-1-4 to TH Leu) in Taiwan, Republic of China.
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Leu, TH., Maa, MC. Tyr-863 phosphorylation enhances focal adhesion kinase autophosphorylation at Tyr-397. Oncogene 21, 6992–7000 (2002). https://doi.org/10.1038/sj.onc.1205904
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DOI: https://doi.org/10.1038/sj.onc.1205904
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