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
G. Manfioletti et al., 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, Molecular and cellular biology, 13(8), 1993, pp. 4976-4985
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.