PDGF-AB requires PDGF receptor alpha-subunits for high-affinity, but not for low-affinity, binding and signal transduction.
There are two PDGF receptor proteins (PDGFR alpha and PDGFR beta) which are proposed to function as subunits to form a high-affinity dimeric PDGF receptor. One aspect of this model about which there is still disagreement is whether PDGF-AB can bind to cells that express only PDGFR beta and, if so, whether PDGF-AB can act as an agonist or an antagonist. To address this question, we derived 3T3 cell lines from Patch mutant mouse embryos in which the PDGFR alpha gene is deleted but which express normal levels of PDGFR beta. Comparison between the binding and response properties of mutant and wild type 3T3 cell lines allowed us to define the contribution that PDGFR alpha makes to the ability of a cell to bind, and respond to, PDGF-AB. We found that PDGF-AB binds to PDGFR alpha-negative 3T3 cells and can induce DNA synthesis, PDGFR beta dimerization, and phosphorylation on tyrosine. In addition we found that PDGF-AB binding and stimulation of these activities is strongly temperature-dependent, whereas PDGF-AB binding and activation of PDGFR beta in the presence of PDGFR alpha is not. However, 3T3 cells that do not express PDGFR alpha require for activation PDGF-AB concentrations that were nearly 100-fold greater than for cells that do express PDGFR alpha. These results suggest that neither PDGF-AA nor PDGF-AB are likely to be physiologically significant activators of cells unless the cells express PDGFR alpha.
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Department of Pathology SJ-60, University of Washington, Seattle 98195.
van Koppen
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Bowen-Pope
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D016475:3T3 Cells; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004622:Embryo, Mammalian; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D013696:Temperature
D010982:Platelet-Derived Growth Factor; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor