Ligand-induced homo- and hetero-dimerization of platelet-derived growth factor alpha- and beta-receptors in intact cells.
Porcine aortic endothelial cells expressing platelet-derived growth factor (PDGF) alpha- or beta-receptors after transfection of the corresponding cDNAs, were used to investigate whether PDGF receptor dimerization occurs in intact cells after ligand binding. Using three different methods--covalent cross-linking of 125I-labeled ligand, cross-linking of metabolically labeled cells after ligand-binding followed by immunoprecipitation, and immunoblotting of cells after ligand binding and cross-linking--it was demonstrated that alpha- as well as beta-receptors form ligand-induced dimeric complexes. Dimerization correlated with induction of receptor kinase activity, measured as receptor autophosphorylation. Heterodimeric complexes could furthermore be induced by PDGF-AB, when added to a mixture of lysates from the alpha- and beta-receptor expressing cell lines, or when added to human fibroblasts which express both receptor types.
Eriksson
A
A
Ludwig Institute for Cancer Research, Uppsala, Sweden.
Rorsman
C
C
Ernlund
A
A
Claesson-Welsh
L
L
Heldin
C H
CH
D000818:Animals; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D013552:Swine
D008024:Ligands; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor