Gas-6

Gas6 (Growth Arrest Specific 6) is one of six structurally unrelated proteins that are secreted 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) . Human Gas6 is a 75 kDa protein that shares 77%-79% aa sequence identity with mouse and rat Gas6. Alternate splicing generates isoforms that lack the Gla domain and/or the spacer between the EGF-like and SHBG regions. 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.