The ras oncogene product p21 is not a regulatory component of adenylate cyclase

Harvey (Ha-MSV) and Kirsten (Ki-MSV) murine sarcoma viruses induce tumours in animals and transform various cells in culture because of the expression of the ras oncogene product, p21 (ref. 1). Proto-oncogenes homologous with these genes are highly conserved evolutionarily 2 and activated ras oncogenes have been detected in many human cancers 3–7 . Whether c- ras oncogenes are directly responsible for human carcinogenesis is uncertain; however, it is clear that p21 mediates virus-induced transformation, although by an unknown mechanism. Epithelial and fibroblast cell lines transformed with Ha-MSV and Ki-MSV express p21 (ref. 8) and exhibit reduced adenylate cyclase activity 9,10 . Like the guanine nucleotide regulatory proteins, N s and N i , which mediate stimulation 11 and inhibition 12 , respectively, of adenylate cyclase, p21 is a membrane-associated GTP binding protein, which exhibits GTPase activity 13–15 . These similarities suggest that p21 and the adenylate cyclase regulatory proteins are related in cellular function, and that p21 depresses adenylate cyclase by inhibiting the activity of N s or acting as N i . We have therefore now examined the structural and functional similarities between p21 and N s and N i and find no evidence that p21 regulates adenylate cyclase activity by acting as one of these regulatory proteins.