Differential regulation of expression of two platelet-derived growth factor receptor subunits by transforming growth factor-beta.
The binding of three radiolabeled isoforms of platelet-derived growth factor (PDGF), 125I-PDGF-AA, 125I-PDGF-AB, and 125I-PDGF-BB, is differentially affected by exposure of quiescent 3T3 cells to transforming growth factor-beta (TGF-beta). By 24 h after exposure to TGF-beta, binding of 125I-PDGF-AA and 125I-PDGF-AB is almost completely lost, whereas binding of 125I-PDGF-BB is reduced by only 40%. The loss of PDGF-binding sites caused by TGF-beta is time- and concentration-dependent and reflects a change in the pattern of expression of receptor subunits; the number of alpha-subunits decreases, and the number of beta-subunits increases. The loss of binding sites for PDGF-AA is accompanied by a decreased mitogenic response to PDGF-AA but not to PDGF-AB or PDGF-BB. These results suggest that TGF-beta may differentially regulate the expression of PDGF-binding sites and the mitogenic responsiveness toward the three PDGF isoforms. TGF-beta did not stimulate synthesis of PDGF A-chain mRNA or PDGF-AA protein, and PDGF-AA receptors could not be restored by the presence of suramin, suggesting that the loss of binding sites may result from direct effects on receptor expression rather than autocrine down-regulation by PDGF-AA.
Gronwald
R G
RG
Department of Pathology, University of Washington, Seattle 98195.
Seifert
R A
RA
Bowen-Pope
D F
DF
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D015342:DNA Probes; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008938:Mitosis; D009693:Nucleic Acid Hybridization; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000235:genetics*; D017479:Receptors, Platelet-Derived Growth Factor; D013498:Suramin / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000494:pharmacology*
D015342:DNA Probes; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D013498:Suramin; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D004247:DNA; D017479:Receptors, Platelet-Derived Growth Factor