THE PROTEIN ENCODED BY A GROWTH ARREST-SPECIFIC GENE (GAS6) IS A NEW MEMBER OF THE VITAMIN-K-DEPENDENT PROTEINS RELATED TO PROTEIN-S, A NEGATIVE COREGULATOR IN THE BLOOD-COAGULATION CASCADE

A set of growth arrest-specific genes (gas) whose expression is negati vely regulated after serum induction has previously been described (C. Schneider, R. M. King, and L. Philipson, Cell 54:787-793, 1988). The detailed analysis of one of them, gas6, is reported here. gas6 mRNA (2 .6 kb) is abundant[y expressed in serum-starved (48 h in 0.5% fetal ca lf serum) NIH 3T3 cells but decreases dramatically after fetal calf se rum or basic fibroblast growth factor stimulation. The human homolog o f gas6 was also cloned and sequenced, revealing a high degree of homol ogy and a similar pattern of expression in IMR90 human fibroblasts. Co mputer analysis of the protein encoded by murine and human gas6 cDNAs showed significant homology (43 and 44% amino acid identity, respectiv ely) to human protein S, a negative coregulator in the blood coagulati on pathway. By using an anti-human Gas6 monospecific affinity-purified antibody, we show that the biosynthetic level of human Gas6 fully ref lects mRNA expression in IMR90 human fibroblasts. This finding thus de fines a new member of vitamin K-dependent proteins that is expressed i n many human and mouse tissues and may be involved in the regulation o f a protease cascade relevant in growth regulation.