Dimerization of B-type platelet-derived growth factor receptors occurs after ligand binding and is closely associated with receptor kinase activation.
Platelet-derived growth factor (PDGF) was found to induce dimerization of purified B-type PDGF receptors, as analyzed by sodium dodecyl sulfate gel electrophoresis after covalent cross-linking using disuccinimidyl suberate. PDGF-BB was 20-fold more effective than PDGF-AB; PDGF-AA was without effect. The dimerization was dose-dependent and was maximal at 0.5-2 micrograms/ml PDGF-BB; at higher concentrations dimerization was less abundant. This indicates that dimerization occurred when one PDGF-BB molecule bound two receptor molecules. The dimerization correlated to activation of the tyrosine kinase of the receptor, determined as autophosphorylation, but was not dependent on phosphorylation reactions because it occurred also in the absence of ATP. Furthermore, dimerization of the receptor correlated with the ability to phosphorylate phosphofructokinase, an exogenous substrate. The complex of ligand and receptor dimer was stable; it resisted electrophoresis under nondenaturing conditions, as well as gel chromatography. The present data indicate that intermolecular mechanisms are involved in signal transduction from the external ligand binding domain to the internal effector domains of the B-type PDGF receptor.
Heldin
C H
CH
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Ernlund
A
A
Rorsman
C
C
Rönnstrand
L
L
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006133:Growth Substances / Q000378:metabolism*; D015151:Immunoblotting; D007700:Kinetics; D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D013552:Swine; D014599:Uterus / Q000378:metabolism
D006133:Growth Substances; D046911:Macromolecular Substances; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D011956:Receptors, Cell Surface; D011494:Protein Kinases; D017479:Receptors, Platelet-Derived Growth Factor