Abl: mechanisms of regulation and activation

The Abl non-receptor tyrosine kinase has been implicated in a wide variety of cellular processes, yet its function and regulation remain poorly understood. Abl has resisted complete understanding not due to lack of interest, but due to the complexity of its overall structure and the corresponding complexity and diversity of its biological activities in the cell. Although Abl consists of many familiar modules with well-understood activities, the ways in which these modules interact are manifold and defy simple categorization. A picture now emerges in which Abl can be potentially regulated in many ways: by phosphorylation, by intramolecular interaction, by interaction with a variety of other proteins, by subcellular localization. Far from being a simple on-off switch, it appears that Abl is better understood as existing in a complex and dynamic equilibrium of states, an equilibrium that can be affected by many signaling inputs. In this review we will discuss the various ways in which the kinase activity of Abl can be regulated; other recent reviews have discussed the larger issue of possible biological roles of Abl (1-3).