The activation mechanism of ACK1 (activated Cdc42-associated tyrosine kinase 1).

摘要: ACK [activated Cdc42 (cell division cycle 42)-associated tyrosine kinase; also called TNK2 (tyrosine kinase, non-receptor, 2)] is activated in response to multiple cellular signals, including cell adhesion, growth factor receptors and heterotrimeric G-protein-coupled receptor signalling. However, the molecular mechanism underlying activation of remains largely unclear. In present study, we demonstrated that interaction SH3 (Src homology 3) domain with EBD [EGFR (epidermal receptor)-binding domain] ACK1 forms an auto-inhibition kinase activity. Release this a key step for ACK1. Mutation caused ACK1, independent suggesting adhesion-mediated through releasing auto-inhibition. A region at N-terminus (Leu 10 –Leu 14 ) essential activation. by EGFR signalling, Grb2 (growth-factor-receptor-bound protein 2) mediates binding activates Furthermore, found mutation Ser 445 proline constitutive Taken together, our studies have revealed novel