Phorbol myristate acetate transactivates the avian β3 integrin gene and induces αvβ3 integrin expression

Hui Jun Zhu, F. Patrick Ross, Xu Cao, Steven L. Teitelbaum

Research output: Contribution to journalArticlepeer-review

Abstract

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) transactivates the avian β3 integrin gene whose promoter contains at least two vitamin D response elements, one of which is in close proximity to a candidate AP1 site (TGACTCA). Since fos/jun and steroid hormones interact to regulate gene expression, we asked whether phorbol-12-myristate-13-acetate (PMA), which stimulates binding of fos/jun to AP1 sites, transactivates the avian β3 integrin gene and, if so, does the phorbol ester modulate 1,25(OH)2D3 induction of the gene. We find the candidate AP1 sequence comigrates with the consensus AP1 sequence on electromobility shift assay when incubated with recombinant c-jun protein. Furthermore, PMA prompts expression of β3 integrin mRNA in the avian monocytic line, HD11. The increase in message reflects transactivation of the β3 gene and is mirrored by plasma membrane appearance of the integrin heterodimer αvβ3. Moreover, attesting to the functional significance of PMA-enhanced αvβ3 expression, cells treated with concentrations of the phorbol ester that induce the β3 gene, spread extensively on plastic, an event blocked by an anti-αv antibody and a peptide mimetic known to inhibit αvβ3-mediated cell attachment. Interestingly, co-addition of 1,25(OH)2D3 and PMA prompts greater expression of αvβ3 than when the cells are exposed to either agent alone and PMA enhances 1,25(OH)2D3-induced β3 integrin mRNA expression. Thus, PMA and 1,25(OH)2D3 impact on the avian β3 integrin gene independently and in combination.

Original languageEnglish (US)
Pages (from-to)420-429
Number of pages10
JournalJournal of cellular biochemistry
Volume61
Issue number3
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • 1,25(OH)D
  • Ap1 site; fos/jun
  • Cell attachment
  • Gene transcription
  • Macrophage-like cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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