Growth arrest-specific gene 6 (Gas6) was initially characterized as a gene whose expression was up-regulated in serum starved NIH 3T3 fibroblasts and whose expression is down-regulated during growth induction. Mouse Gas6 is a 673 amino acid protein that shares 81% identity to its human homolog. Gas6 is a member of the vitamin K-dependent family of proteins that includes human protein S, a negative coregulator in the blood coagulation pathway. Gas6 and protein S share structural motifs that characterize this family: an extensively gamma -carboxylated amino terminus (Gla domain), four EGF-like repeats, and a carboxy terminus containing globular (G) domains with homology to steroid hormone-binding globulin. It is a ligand for the Axl (Ufo/Ark), Sky (Dtk/Tyro3/Rse/Brt/Tif), and Mer (Eyk) families of tyrosine kinase receptors. Gas6 binds to these receptors via tandem G domains at its C-terminus. Gas6 is ubiquitously expressed, but most abundantly in lung, intestine, bone marrow and endothelium.
Gas6 has been implicated in a variety of biological processes. It serves as a mitogen for fibroblasts, endothelial cells, neural cells, vascular smooth muscle cells and several tumor-derived cell lines. In addition, Gas6 prevents apoptosis, independent of its mitogenic activity. Gas6 is capable of inducing cell adhesion and chemotaxis in specific cell types. It also supports vitamin K-independent hematopoiesis when expressed by stromal cells. Gas6 signal transduction following Axl/Sky/Mer receptor activation has been reported to occur through such diverse signaling pathways as PI3K, MAP kinase, Src, Ras and beta -catenin.
