Platelet-derived growth factor (PDGF) α receptor activation modulates the calcium mobilizing activity of the PDGF β receptor in Balb/c3T3 fibroblasts

Pamela A. Diliberto, Gerald W. Gordon, Chun Li Yu, H. Shelton Earp, Brian Herman

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41 Scopus citations

Abstract

In order to determine whether distinct platelet-derived growth factor (PDGF) receptors (α and β) 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 ≥ AB ≥ AA. All cells were BB-PDGF-responsive, but only 74% of cells examined responded to AA-PDGF. The Ca2+, 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 α 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-in-duced 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 AlF4--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+, response. The inhibition of the BB-PDGF Ca2+, 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 α receptor-mediated response as assessed by AA-PDGF-induced increases in Ca2+i, whereas all cells possess the β receptor-mediated responses; and (b) AA-PDGF and its associated α receptor can modulate the activity of the β receptor through a mechanism that is dependent upon Ca2+-influx which may be controlled in part by PKC activation.

Original languageEnglish (US)
Pages (from-to)11888-11897
Number of pages10
JournalJournal of Biological Chemistry
Volume267
Issue number17
StatePublished - Jun 15 1992

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