Cellular response to platelet-derived growth factor (PDGF)-AB after down-regulation of PDGF alpha-receptors. Evidence that functional binding does not require alpha-receptors.
Platelet-derived growth factor (PDGF) and its receptor exist in multiple forms. PDGF exists in three dimeric combinations of A and B subunit chains, which are the products of separate genes. The PDGF receptor is similarly encoded by genes for two distinct receptor proteins, alpha and beta. A recent model proposed PDGF binding involves the association of the two receptor proteins into three possible dimeric forms. An essential prediction of that model is that PDGF alpha-receptors are required for cells to bind and respond to the heterodimeric AB isoform of PDGF. In contrast, we found both binding and functional response to PDGF-AB was retained in Balb/c-3T3 cells after PDGF alpha-receptors had been down-regulated by PDGF-AA pretreatment. The observation that PDGF-AB could still elicit these responses suggests that at 37 degrees C, PDGF-AB may bind directly to beta-receptors in either monomeric or dimeric forms and that initial receptor activation may occur independently of the formation of alpha beta-receptor heterodimers.
Drozdoff
V
V
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Pledger
W J
WJ
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D015536:Down-Regulation; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D014158:Transcription, Genetic
D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor