Transcriptional regulation of the A and B chain genes of platelet-derived growth factor in microvascular endothelial cells

W. M. Kavanaugh, G. R. Harsh IV, N. F. Starksen, C. M. Rocco, L. T. Williams

Research output: Contribution to journalArticlepeer-review

Abstract

Platelet-derived growth factor is expressed as dimers of two homologous polypeptide chains, termed A and B, encoded by different genes. A and B chain mRNA levels in microvascular endothelial cells are increased by phorbol ester, thrombin, and transforming growth factor-β (TGF-β) and are reduced by agents that elevate cyclic AMP. In this report, we investigated the effects of these regulatory agents on A and B chain transcription rates. By nuclear run-on analysis, TGF-β stimulated transcription of both A and B chain genes. Thrombin and phorbol ester stimulated B chain transcription and had little or no detectable effect on A chain transcription. Pretreatment of cultures with 50 μM forskolin, a potent activator of adenylyl cyclase, completely blocked B chain transcription by thrombin and TGF-β, but did not inhibit A chain transcription induced by TGF-β. These results show that expression of platelet-derived growth factor mRNA involves both positive and negative transcriptional regulation and that there are differences in the transcriptional control of the A and B chain genes.

Original languageEnglish (US)
Pages (from-to)8470-8472
Number of pages3
JournalJournal of Biological Chemistry
Volume263
Issue number17
StatePublished - 1988
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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