Regulation of Ack-Family Nonreceptor Tyrosine Kinases

Abstract EN

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.