Activated Cdc42 (cell division cycle 42)-associated tyrosine kinase (ACK1; EC 2.7.10.2), also called TNK2 (tyrosine kinase, non-receptor, 2) is activated in response to multiple cellular signals, including cell adhesion, growth factor receptors and heterotrimeric GPCR-signaling. interaction of the SH3 (Src homology 3) domain with the EBD (EGFR-binding domain) in ACK1 forms an auto-inhibition of the kinase activity. Release of this auto-inhibition is a key step for activation of ACK1. Mutation of the SH3 domain caused activation of ACK1, independent of cell adhesion, suggesting that cell adhesion-mediated activation of ACK1 is through releasing the auto-inhibition. ACK is amplified and overexpressed in multiple cancers, and associated with tumour progression through promoting cell growth and migration.