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Regulation of AP‐1 Activity in Glucose‐Stimulated Insulinoma Cells
Author(s) -
Müller Isabelle,
Endo Takeshi,
Thiel Gerald
Publication year - 2010
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/jcb.22715
Subject(s) - insulinoma , downregulation and upregulation , extracellular , protein kinase a , stimulation , cytoplasm , chemistry , microbiology and biotechnology , biology , kinase , insulin , endocrinology , gene , biochemistry
The transcriptional activity of AP‐1 has been analyzed in glucose‐stimulated INS‐1 insulinoma cells using a chromosomally embedded AP‐1‐responsive reporter gene. We show that AP‐1 activity was significantly elevated in glucose‐treated INS‐1 cells. Preincubation of the cells with nifedipine or expression of the Ca 2+ binding protein parvalbumin in the cytoplasm of INS‐1 cells reduced AP‐1 activity. Thus, activation of L ‐type Ca 2+ channels and an elevated cytoplasmic Ca 2+ concentration are crucial to connecting glucose stimulation with enhanced AP‐1 activity. Expression of dominant negative forms of A‐Raf, MKK4 or MKK6 and pharmacological inhibition of MEK and p38 revealed that extracellular signal‐regulated protein kinase, p38 and c‐Jun NH 2 ‐terminal protein kinase participate in the upregulation of AP‐1 activity. Expression of dominant‐negative mutants of c‐Jun and Elk‐1 reduced AP‐1 transcriptional activity in INS‐1 cells indicating that c‐Jun and ternary complex factors are involved in the regulation of AP‐1 activity in glucose‐stimulated insulinoma cells. J. Cell. Biochem. 110: 1481–1494, 2010. © 2010 Wiley‐Liss, Inc.