Functional co-operation between the subunits in heterodimeric platelet-derived growth factor receptor complexes

To determine the importance of the phosphorylation capacity of receptor kin ase as well as the ability to serve as docking sites for SH2-domain-contain ing signal transduction molecules, we established pig aortic endothelial ce ll lines stably expressing kinase-active platelet-derived growth factor (PD GF) cc-receptors together with kinase-inactive P-receptors, and vice versa. After stimulation with PDGF-AB, heterodimeric receptor complexes were form ed in which the kinase-inactive receptor was phosphorylated by the kinase-a ctive receptor, although less efficiently than in heterodimers of wild-type receptors. The kinase-active receptor was only minimally phosphorylated. T hus the phosphorylation within the receptor dimer occurred in trans between the components. Analyses of the abilities of heterodimeric receptor comple xes of one kinase-active and one kinase-inactive receptor to mediate mitoge nicity, chemotaxis and activation of mitogen-activated protein kinase revea led less efficient effects than those of heterodimers of wild-type receptor s. Importantly, however, the fact that signalling capacities were retained illustrates a functional co-operation between the two receptor molecules in the dimer, where one receptor provides a functional kinase and the other a cts as a substrate and provides docking sites for downstream signalling mol ecules.