REM IS A NEW MEMBER OF THE RAD-RELATED AND GEM KIR RAS-RELATED GTP-BINDING PROTEIN FAMILY REPRESSED BY LIPOPOLYSACCHARIDE/

We report the cDNA cloning and characterization of a novel GTP-binding protein, termed Rem (for Rad and Gem-related), that was identified as a product of polymerase chain reaction amplification using oligonucle otide primers derived from conserved regions of the Rad, Gem, and Kir Ras subfamily, Alignment of the full-length open reading frame of mous e Rem revealed the encoded protein to be 47% identical to the Rad, Gem , and Kir proteins, The distinct structural features of the Rad, Gem, and Kir subfamily are maintained including a series of nonconservative amino acid substitutions at positions important for GTPase activity a nd a unique sequence motif thought to direct membrane association. Rec ombinant Rem binds GTP in a specific and saturable manner, Ribonucleas e protection analysis found Rem to be expressed at comparatively high levels in cardiac muscle and at moderate levels in lung, skeletal musc le, and kidney, The administration of lipopolysaccharide to mice, a po tent activator of the inflammatory and immune systems, results in the general repression of Rem mRNA levels in a dose-and time-dependent man ner, Thus, Rem is the first Ras-related gene whose mRNA levels have be en shown to be regulated by repression.