A NOVEL GTP-BINDING PROTEIN WHICH IS SELECTIVELY REPRESSED IN SV40-TRANSFORMED FIBROBLASTS

We have used a subtractive hybridization procedure to isolate cDNA clo nes for proteins that are produced by human fibroblasts, but not by th eir SV40-transformed counterparts. With this technique we found, in ad dition to fibronectin and collagen VI, a novel GTP-binding protein. Se quencing of overlapping cDNA clones demonstrated that this protein is composed of 364 amino acids with a molecular mass of 41 kDa and a calc ulated isoelectric point of 9.4. It contains the five sequence motifs G1-G5 that are conserved in all GTP binding proteins. Apart from these characteristic motifs the amino acid sequence differs substantially f rom those of the well characterized G-proteins, but it is similar to t hose of some recently identified proteins from Caenorhabditis elegans, from Schizosaccharomyces pombe, and from an archaebacterium, suggesti ng the existence of a new subfamily within the superfamily of the GTP- binding proteins. The striking conservation of the primary structure b etween distantly related species indicates a fundamental function of t he new protein. Since it is produced in normal, but not in virally tra nsformed fibroblasts, it may play a role in the expression of the tran sformed phenotype or in growth control.