Regulation of integrins by RAP1

RAP1 is a close relative of RAS that controls cell adhesion by regulating integrins. The effector of RAP1 that regulates integrins is RAP1 interacting adapter molecule (RIAM) which we showed is required for lymphocyte trafficking. In collaboration with Jinhua Wu (Fox Chase Cancer Center), using fluorescent reporters and X-ray crystallography we have shown that the RA-PH domain of RIAM functions as an AND-gate to bind activated RAP1 and PIP₂ and that the binding of RAP1 to RIAM is regulated by phosphorylation of tyrosine 45 in the N-terminal domain of RIAM. Current studies are aimed at identifying other molecules that associate with RIAM to modulate the activation complex. 

Activation of LFA-1 by RAP1 is mediated by RIAM

The RIAM RA-PH regions fold into a dual function domain