activated Cdc42-associated Kinase 1

ACK1 (activated Cdc42-associated kinase 1) is a nonreceptor tyrosine kinase and the only tyrosine kinase known to interact with Cdc42. ACK1 phosphorylates and activates the guanine nucleotide exchange factor Dbl, which in turn directs the Rho family GTP-binding proteins (1).  ACK1 interacts most strongly with the SH3 domains of Src family kinases (Src or Hck) via its C-terminal proline-rich domain. The ACK1 interacts most strongly with the SH3 domains of Src family kinases (Src or Hck) by its C-terminal praline rich domain. ACK1 also acts as a regulator of Dbl, which in turn activates Rho family proteins. There are at least 2 ACK1 associated proteins (Cdc42 and Grb) that are required for ACK1-dependent EGF signaling in the cell. The central motif in ACK1 has a clatherin adaptor that colocalizes ACK1 with in the clatherin containing vesicles that are involved in the trafficking of receptor mediated endocytosis (2). The ACK family of non-receoptortyrosine kinase (ACK1 and ACK2) specifically associate with Cdc42 to modulate its activity in several signaling pathways. ACK1 acts as a mediator of EGF signal to Rhofamily GTP-binding proteins (3). The activation of ACK1 nvolves autophoshorylation at Tyrosine 284, upon phosphorylation, the ACK1 activity is significantly enhanced. Tyrsine substitution at 284 by Phenylalnine (Y284F) and expression in COS-7 cells exhibit dramatically reduced levels of tyrosine phosphorylation (1). ACK2 mediates cell adhesion signals initialted by integrins