Regulation of Abl kinases by adaptor proteins Review

The kinase activity of c-Abl is known to be tightly regulated. Mechanisms of c-Abl kinase regulation can be classified as intramolecular or intermolecular interactions. Crystallization of the amino (N)-terminal region of c-Abl has revealed that intramolecular folding of the N terminus onto the kinase domain represses intrinsic kinase activity. With regard to intermolecular interactions, recent studies suggested that trans-acting molecules bind to a proline-rich (PR) regions in the carboxyl (C)-terminal portion of c-Abl and activate the kinase. In this review, we focus on c-Abl kinase activation and the mechanisms of substrate phosphorylation mediated by adaptor molecules which bind to the C-terminal PR regions of c-Abl kinase.