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

✍ Scribed by Hui-Jun Zhu; F. Patrick Ross; Xu Cao; Steven L. Teitelbaum

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 906 KB
• Volume: 61
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19960601)61:3<420::aid-jcb9>3.0.co;2-v

✦ Synopsis

1,25-Dihydroxyvitamin D3 (1,25(0H),D3) transactivates the avian p3 integrin gene whose promoter contains at least two vitamin D response elements, one of which is in close proximity to a candidate API site (TGACTCA). Since fosljun and steroid hormones interact to regulate gene expression, we asked whether phorbol-12myristate-13-acetate (PMA), which stimulates binding of fosljun to API sites, transactivates the avian p3 integrin gene and, if so, does the phorbol ester modulate 1 ,25(OH)2D3 induction of the gene. We find the candidate API sequence comigrates with the consensus AP1 sequence on electromobility shift assay when incubated with recombinant c-jun protein. Furthermore, PMA prompts expression of p3 integrin mRNA in the avian monocytic line, H D I 1. The increase in message reflects transactivation of the p3 gene and is mirrored by plasma membrane appearance of the integrin heterodimer a& . Moreover, attesting to the functional significance of PMA-enhanced avP3 expression, cells treated with concentrations of the phorbol ester that induce the p3 gene, spread extensively on plastic, an event blocked by an anti-a, antibody and a peptide mimetic known to inhibit a,p3-mediated cell attachment. Interestingly, co-addition of 1 ,25(OH)2D3 and PMA prompts greater expression of a,p3 than when the cells are exposed to either agent alone and PMA enhances 1,25(0H),D3-induced p3 integrin mRNA expression. Thus, PMA and 1,25(OH)2D3 impact on the avian p3 integrin gene independently and in combination.