Roles of γ‐carboxylation and a sex hormone‐binding globulin‐like domain in receptor‐binding and in biological activities of Gas6

Abstract
Gas6 is a ligand for an Axl/Sky receptor tyrosine kinase subfamily and has a structure composed of a Gla domain, four EGF‐like domains and a C‐terminal sex hormone‐binding globulin (SHBG)‐like domain. When examining the role of each domain in receptor‐binding and biological activities of Gas6, we found that receptor‐binding and mitogenic activities were markedly reduced by inhibiting γ‐carboxylation of the Gla domain, while a Gas6 mutant composed of only an SHBG‐like domain retained both of these activities. Thus, the SHBG‐like domain is apparently an entity indispensable for Gas6 activities, and γ‐carboxylation of the Gla domain has a regulatory role in retaining the activity of native Gas6.