RAP1 P21 REGULATES THE INTERACTION OF RAS P21 WITH RGL, A NEW EFFECTOR PROTEIN OF RAS P21

We have recently found that ralGDS family members (RGL and ralGDS) are putative effector proteins of ras p21. rap1 p21 is a small GTP-binding protein which has the same amino acid sequence as the effector loop of ras p21, We examined the effect of rap1 p21 on the interaction of ras p21 with RGL. The GTP-bound form of rap1 p21 interacted with RGL as well as did ras p21, rap1 p21 inhibited the interaction of ras p21 with RGL. RGL was phosphorylated by cyclic AMP-dependent protein kinase (protein kinase A), Phosphorylation of RGL did not affect its binding to ras p21 and rap1 p21 under the conditions that phosphorylation of Raf-1 reduced its affinity for ras p21. These results demonstrate that rap1 p21 but not protein kinase A regulates the interaction of ras p21 with RGL and suggest that rap1 p21 and protein kinase A may cooperate to distinguish the signal of ras p21 to RGL from that to Raf-1.