THE PRODUCT OF A GAS6 SPLICE VARIANT ALLOWS THE RELEASE OF THE DOMAINRESPONSIBLE FOR AXL TYROSINE KINASE RECEPTOR ACTIVATION

The product of gas6 (Gas6) is a growth factor with high level of simil arity to protein S and was identified as the ligand for Axl family of tyrosine kinase receptors, Gas6 contains an N-terminal gamma-carboxyla ted domain (Gla), four epidermal growth factor like domains and a larg e C-terminal D region, An alternative Gas6 spliced form (Gas6SV) havin g an additional 43 amino acids between fourth EFG like and D domain wa s characterised, Here we show data indicating that Gas6SV is specifica lly cleaved within the inserted sequence, thereby splitting the D doma in from the remaining part of the protein, The resulting two proteolyt ic products of 36 kDa and 50 kDa were separated and the 50 kDa fragmen t corresponding to region D was shown to be responsible for Axl recept or activation, Furthermore a deletion mutant of Gas6 containing only t he D domain was shown to similarly activate Art receptor phosphorylati on unequivocally demonstrating that D domain can act as a signalling m olecule, The possible roles of the proteolytic processing of Gas6SV in the regulation of growth factor availability are discussed, (C) 1997 Federation of European Biochemical Societies.