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c‐Jun and JunB Are Essential for Hypoglycemia‐Mediated VEGF Induction
Author(s) -
TEXTOR BJÖRN,
SATORSCHMITT MELANIE,
RICHTER KARL HARTMUT,
ANGEL PETER,
SCHORPPKISTNER MARINA
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.076
Subject(s) - junb , transcription factor , mapk/erk pathway , signal transduction , kinase , chemistry , microbiology and biotechnology , c jun , biology , endocrinology , medicine , biochemistry , gene
Physiological conditions like hypoxia or hypoglycemia trigger expression of VEGF, a key regulator of angiogenesis. To elucidate the molecular mechanism underlying the VEGF regulation of hypoglycemia, we investigated the role of AP‐1 transcription factor subunits c‐Jun and JunB. Using c‐jun −/− and junB −/− mouse embryonic fibroblasts, we demonstrate that both c‐Jun and JunB are required for the hypoglycemia‐mediated induction of VEGF expression. This process is independent of the master regulator of hypoxic stress HIF‐1, as HIF expression and stabilization are not affected by the loss of AP‐1 subunits. Analysis of signaling cascades regulating c‐Jun and/or JunB activity and/or transcription upon hypoglycemia by application of specific inhibitors of protein kinase C (PKC) or extracellular signal‐regulated kinase (ERK) signaling revealed that hypoglycemia‐mediated induction of c‐Jun is regulated via a PKCα‐dependent signaling pathway. In contrast, JunB is activated by the MAP kinase ERK for the AP‐1 subunits c–Jun and JunB to mediate VEGF regulaltion of hypoglycemia.