MOLECULAR-CLONING AND CHARACTERIZATION OF A RAT HOMOLOG OF CAP, THE ADENYLYL CYCLASE-ASSOCIATED PROTEIN FROM SACCHAROMYCES-CEREVISIAE

We have isolated a rat cDNA whose expression suppresses the physiologi cal consequences of the chromosomal disruption of CAP, the gene encodi ng the adenylyl cyclase-associated protein of Saccharomyces cerevisiae . Yeast CAP is a bifunctional protein: the NH2 terminus is necessary a nd sufficient for cellular responsiveness to activated RAS proteins, w hile the COOH terminus is required for normal cellular morphology and growth control. The rat MCH1 cDNA encodes a protein of 474 amino acids that is 36% identical to S. cerevisiae CAP and is capable of suppress ing the loss of the COOH-terminal functions of CAP when expressed in y east. The MCH1 protein therefore appears to be a structural and functi onal homolog of the yeast cyclase-associated proteins. Northern analys is of MCH1 gene expression shows it to be constitutively expressed in all cell and tissue types examined. The cloning of a rat homolog of CA P, in addition to the cloning of a human CAP homolog by Matviw et al. (Matviw, H., Yu, G., and Young, D. (1992) Mol. Cell. Biol. 12, 5033-50 40), demonstrates that both cyclase-associated proteins and their func tions may have evolved with mammalian cells.