Table of Contents
Journal of Signal Transduction
Volume 2011, Article ID 742372, 9 pages
Review Article

Regulation of Ack-Family Nonreceptor Tyrosine Kinases

Department of Physiology and Biophysics, School of Medicine, Stony Brook University, Basic Science Tower T5, Nicolls Road, Stony Brook, NY 11794, USA

Received 30 November 2010; Accepted 13 January 2011

Academic Editor: Yasuo Fukami

Copyright © 2011 Victoria Prieto-Echagüe and W. Todd Miller. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.