The related Axl, Sky and Mer receptor tyrosine kinases (RTKs) are increasingly being implicated in a host of discrete cellular responses including cell survival, proliferation, migration and phagocytosis. Furthermore, their ligands Gas6 and protein S are characteristically dependent on vitamin K for expression of their functions. The Gas6/Axl system is implicated in several types of human cancer as well as inflammatory, autoimmune, vascular and kidney diseases. Each member of the Axl RTK subfamily possesses distinct expression profiles as well as discrete functions. In this article, we review the knowledge so far on the intracellular signalling interactions and pathways concerning each of the Axl RTKs. In this way, we hope to gain a greater understanding of the mechanisms that set each of them apart, and that relay their associated functions. (c) 2006 Elsevier Ltd. All rights reserved.