GAS-6 is a multimodular protein that is up-regulated by a wide variety of cell types in response to growth arrest . Gas6 and the structurally related Protein S are vitamin K-dependent and have an extensively gamma -carboxylated N-terminal Gla domain, four EGF-like repeats, and a C-terminal region with homology to steroid hormone binding globulin (SHBG) . Gas6 binds and induces signaling through the receptor tyrosine kinases Axl, Dtk, and Mer . Human Gas6 interacts with both mouse and rat orthologs of these receptors . The full length isoform may be cleaved, resulting in release of the free SHBG region which can independently activate Axl . Shed soluble forms of Axl and Mer bind Gas6 and function as decoy receptors . Gas6 induces a variety of responses, including prevention of apoptosis , cell proliferation , platelet-mediated thrombosis , retinal epithelial cell phagocytosis of outer rod segments , inhibition of VEGF-induced endothelial cell chemotaxis , and the differentiation and expansion of NK cell precursors . The affinity of Gas6 for phosphatidylserine likely contributes to its role in promoting the phagocytosis of apoptotic cells . Several of these effects have been shown to require gamma -carboxylation of the Gla domain .
