title: Regulation of ack-family nonreceptor tyrosine kinases.
abstract: Ack family non-receptor tyrosine kinases are unique with regard to their domain composition and regulatory properties. Human Ack1 (activated Cdc42-associated kinase) is ubiquitously expressed and is activated by signals that include growth factors and integrin-mediated cell adhesion. Stimulation leads to Ack1 autophosphorylation and to phosphorylation of additional residues in the C-terminus. The N-terminal SAM domain is required for full activation. Ack1 exerts some of its effects via protein-protein interactions that are independent of its kinase activity. In the basal state, Ack1 activity is suppressed by an intramolecular interaction between the catalytic domain and the C-terminal region. Inappropriate Ack1 activation and signaling has been implicated in the development, progression, and metastasis of several forms of cancer. Thus, there is increasing interest in Ack1 as a drug target, and studies of the regulatory properties of the enzyme may reveal features that can be exploited in inhibitor design.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Stony Brook University, Basic Science Tower T5, Nicolls Road, Stony Brook, NY 11794, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Prieto-Echagüe
authors.forename: W Todd
authors.initials: WT
authors.lastname: Miller