A SMALL GTP-BINDING PROTEIN, RHO, ASSOCIATES WITH THE PLATELET-DERIVED GROWTH-FACTOR TYPE-BETA RECEPTOR UPON LIGAND-BINDING

Ligand binding to the platelet-derived growth factor (PDGF) receptor i nitiates a complex and diverging cascade of signaling pathways. GTP-bi nding proteins with intrinsic GTPase activity (G-proteins) frequently link cell surface receptors to intracellular signaling pathways, but n o close associations of the PDGF receptor and any small G-proteins, no r any such associations activated by ligand binding to the receptor ha ve been previously reported. We demonstrate that a small GTP-binding p rotein binds specifically to the murine and human PDGF type-beta recep tor. In response to PDGF-BB stimulation, there is an increase in the a mount of labeled small G-protein associated with the PDGF type-beta re ceptor. The GTP-binding protein did not undergo ligand-induced associa tion with a mutant receptor protein that was unable to bind ATP. Prote olytic cleavage analysis, together with two dimensional separation tec hniques, identified the small G-protein specifically associating with the PDGF type-beta receptor after ligand binding as a member of the Rh o family. This was confirmed by demonstration that the small G-protein coimmunoprecipitated by the anti-PDGF receptor antibody was a substra te for the ADP-ribosyltransferase C3 exoenzyme. Thus, the PDGF type-be ta receptor may form a complex with one or more small G-proteins upon binding PDGF-BB, and the Rho small G-protein is likely to be an import ant component of the proteins making up the multimeric signaling compl ex of the PDGF type-beta receptor.