Functional co-operation between the subunits in heterodimeric platelet-derived growth factor receptor complexes.
To determine the importance of the phosphorylation capacity of receptor kinase as well as the ability to serve as docking sites for SH2-domain-containing signal transduction molecules, we established pig aortic endothelial cell lines stably expressing kinase-active platelet-derived growth factor (PDGF) alpha-receptors together with kinase-inactive beta-receptors, and vice versa. After stimulation with PDGF-AB, heterodimeric receptor complexes were formed in which the kinase-inactive receptor was phosphorylated by the kinase-active receptor, although less efficiently than in heterodimers of wild-type receptors. The kinase-active receptor was only minimally phosphorylated. Thus the phosphorylation within the receptor dimer occurred in trans between the components. Analyses of the abilities of heterodimeric receptor complexes of one kinase-active and one kinase-inactive receptor to mediate mitogenicity, chemotaxis and activation of mitogen-activated protein kinase revealed less efficient effects than those of heterodimers of wild-type receptors. 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 acts as a substrate and provides docking sites for downstream signalling molecules.
Ludwig Institute for Cancer Research, Box 595, Biomedical Center, S-751 24 Uppsala, Sweden.
M
M
Emaduddin
S
S
Ekman
L
L
Rönnstrand
C H
CH
Heldin
D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D017931:DNA Primers; D019281:Dimerization; D004789:Enzyme Activation; D008934:Mitogens / Q000494:pharmacology; D010449:Peptide Mapping; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine; D014443:Tyrosine / Q000378:metabolism
D017931:DNA Primers; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D014443:Tyrosine; D017479:Receptors, Platelet-Derived Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases