Key points are not available for this paper at this time.
In order to determine whether distinct platelet-derived growth factor (PDGF) receptors (alpha and beta) can modulate the activity of one another, PDGF isoform (AA, BB, and AB)-stimulated changes in Ca2+i were monitored by digitized video microscopy in single cells upon sequential addition of PDGF isoforms. In Balb/c 3T3 fibroblasts, all PDGF isoforms were capable of stimulating increases in Ca2+i of 200-600% above basal levels, although with different potencies: BB greater than or equal to AB greater than AA. All cells were BB-PDGF-responsive, but only 74% of cells examined responded to AA-PDGF. The Ca2+i response elicited by BB-PDGF was inhibited by 60-75% in cells stimulated 10 min earlier with the AA isoform. The half-life of this inhibition was 22 min. In cells in which the alpha receptor was down-regulated by prolonged incubation with AA-PDGF, BB-induced Ca2+i responses were not inhibited. Pretreatment of cells with phorbol ester did not inhibit BB-PDGF-induced increases in Ca2+i, yet down-regulation of PKC activity prevented the AA-PDGF inhibition of BB-PDGF-induced Ca2+i responses. An increase in Ca2+i induced by AlF(4-)-stimulated IP3 generation did not inhibit a subsequent BB-PDGF Ca2+i response; however, attenuation of AA-PDGF-induced extracellular Ca2+ influx with EGTA prevented the inhibition of BB-PDGF-induced Ca2+i increases. Readdition of Ca2+ to the medium after removal of EGTA restored the inhibition of the BB-PDGF Ca2+i response. The inhibition of the BB-PDGF Ca2+i response by AA-PDGF was not caused by inhibition of PDGF receptor tyrosine autophosphorylation, which was unchanged after pretreatment with AA-PDGF. These results demonstrate: (a) that only a subpopulation of cells possess a functional alpha receptor-mediated response as assessed by AA-PDGF-induced increases in Ca2+i, whereas all cells possess the beta receptor-mediated responses; and (b) AA-PDGF and its associated alpha receptor can modulate the activity of the beta receptor through a mechanism that is dependent upon Ca(2+)-influx which may be controlled in part by PKC activation.
Diliberto et al. (1992) studied this question.