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 initiates a complex and diverging cascade of signaling pathways. GTP-binding proteins with intrinsic GTPase activity (G-proteins) frequently link cell surface receptors to intracellular signaling pathways, but no close associations of the PDGF receptor and any small G-proteins, nor any such associations activated by ligand binding to the receptor have been previously reported. We demonstrate that a small GTP-binding protein binds specifically to the murine and human PDGF type-beta receptor. In response to PDGF-BB stimulation, there is an increase in the amount of labeled small G-protein associated with the PDGF type-beta receptor. The GTP-binding protein did not undergo ligand-induced association with a mutant receptor protein that was unable to bind ATP. Proteolytic cleavage analysis, together with two-dimensional separation techniques, identified the small G-protein specifically associating with the PDGF type-beta receptor after ligand binding as a member of the Rho family. This was confirmed by demonstration that the small G-protein coimmunoprecipitated by the anti-PDGF receptor antibody was a substrate for the ADP-ribosyltransferase C3 exoenzyme. Thus, the PDGF type-beta 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 important component of the proteins making up the multimeric signaling complex of the PDGF type-beta receptor.
Zubiaur
M
M
Cancer Research Center, Boston University School of Medicine, Massachusetts 02118, USA.
Sancho
J
J
Terhorst
C
C
Faller
D V
DV
D016475:3T3 Cells; D000818:Animals; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D051379:Mice; D011233:Precipitin Tests; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000276:immunology / Q000378:metabolism*
D006160:Guanosine Triphosphate; D017479:Receptors, Platelet-Derived Growth Factor; D019204:GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras)