Effects of the ras-related rap2 protein on cellular proliferation.

Ras oncogenes encode 21-kDa (p21s) GTP binding proteins that are capable of transforming immortalized cells in culture. The ras-related rap1A/Krev-1/smgp21A protein, that exhibits a similar structural organization and contains the same effector domain as ras proteins, antagonizes ras-transformation. In order to investigate whether the closely related (61% identical) rap2 protein had similar capacities, the corresponding cDNA was inserted into constitutive as well as inducible mammalian expression vectors. Neither the wild-type, nor an "activated" mutant carrying a glycine-to-valine substitution at position 12, had any transforming activity. Several independent lines of evidence demonstrate that the rap2 protein exhibits neither growth-promoting nor growth-inhibitory effects, and that its over-expression does not interfere with ras-induced transformation. Thus, in spite of their great similarities, the rap1A/Krev-1/smgp21A and rap2 proteins have distinct physiological properties.