Journal
FEBS LETTERS
Volume 468, Issue 1, Pages 53-58Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(00)01181-9
Keywords
hypoxia; hypoxia-inducible factor-1 (HIF-1); extracellular regulated kinase 1 and 2 (ERK)
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Hypoxia-inducible factor-1 (HIF-1) is a transcription factor activated by hypoxia, The HIF-1 activation transduction pathway is poorly understood. In this report, we investigated the activation of extracellular regulated kinases (ERK) in hypoxia and their involvement in HIF-1 activation. We demonstrated that in human microvascular endothelial cells-1 (HMEC-1), ERK kinases are activated during hypoxia, Using dominant negative mutants, we showed that ERK1 is needed for hypoxia-induced HIT-1 transactivation activity. Moreover, using a kinase assay and Western blot experiments, we showed that HIF-1 alpha is phosphorylated in hypoxia by an ERK-dependent pathway. These results evidence the role of mitogen-activated protein kinase in the transcriptional response to hypoxia, (C) 2000 Federation of European Biochemical Societies.
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