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Phorbol myristate acetate transactivates the avian β 3 integrin gene and induces α v β 3 integrin expression
Author(s) -
Zhu HuiJun,
Ross F. Patrick,
Cao Xu,
Teitelbaum Steven L.
Publication year - 1996
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19960601)61:3<420::aid-jcb9>3.0.co;2-v
Subject(s) - transactivation , ap 1 transcription factor , microbiology and biotechnology , phorbol , gene expression , biology , integrin , beta (programming language) , gene , biochemistry , signal transduction , cell , protein kinase c , computer science , programming language
1,25‐Dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) transactivates the avian β 3 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 β 3 integrin gene and, if so, does the phorbol ester modulate 1,25(OH) 2 D 3 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 β 3 integrin mRNA in the avian monocytic line, HD11. The increase in message reflects transactivation of the β 3 gene and is mirrored by plasma membrane appearance of the integrin heterodimer α v β 3 . Moreover, attesting to the functional significance of PMA‐enhanced α v β 3 expression, cells treated with concentrations of the phorbol ester that induce the β 3 gene, spread extensively on plastic, an event blocked by an anti‐α v antibody and a peptide mimetic known to inhibit α v β 3 ‐mediated cell attachment. Interestingly, co‐addition of 1.25(OH) 2 D 3 and PMA prompts greater expression of α v β 3 than when the cells are exposed to either agent alone and PMA enhances 1,25(OH) 2 D 3 ‐induced β 3 integrin mRNA expression. Thus, PMA and 1,25(OH) 2 D 3 impact on the avian β 3 integrin gene independently and in combination. © 1996 Wiley‐Liss, Inc.