ACK, Active

ACK is a tyrosine kinase that binds CDC42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of CDC42Hs (1). Overexpression of ACK in cancer cell lines of epithelial origin increases cellular motility and invasiveness. In a mouse model, ACK overexpression enhances the ability of a human breast cancer cell line to metastasize to the lung and increased mortality (2). Ligand stimulation of alpha-3 beta-1 integrin leads to activation of ACK which then enhances p130CAS phosphorylation and activation of RAC.