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 rap 1A/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 rap 1A/Krev‐1/smgp21A and rap2 proteins have distinct physiological properties.