Phosphorylation of rap Proteins by the cAMP-Dependent Protein Kinase

Abstract

The products of rap genes (rap1A, rap1B, rap2A, rap2B) are small molecular weight GTP-binding proteins that exhibit striking similarities with ras p21s1–4. In particular, ras and rap proteins share a conserved “effector” region spanning residues 32–42 through which ras-p21s are thought to exert their biological effects; they also have a C-terminal CAAX sequence (where A is an aliphatic residue and X any amino acid) responsible for posttranslational modification and membrane binding of ras proteins5. The identity of the “effector” domain between ras and rap proteins had suggested that rap proteins could antagonize the activity of ras proteins by competing for a common effector. Independently, M. Noda’s group isolated a cDNA, Krev-1, whose overexpression could revert the transformed phenotype of Kirsten sarcoma-virus transformed NIH 3T3 cells6; the sequence of the Krev-1 protein was identical to that of the rap1A protein. Moreover, in vitro, the rap1A protein has been shown to be able to compete efficiently with ras p21 for interaction with GAP7(GTPase Activating protein), which may constitute the effector of ras p218–12.