PMID- 10683440 OWN - NLM STAT- MEDLINE DCOM- 20000410 LR - 20190621 IS - 0014-5793 (Print) IS - 0014-5793 (Linking) VI - 468 IP - 1 DP - 2000 Feb 18 TI - ERK activation upon hypoxia: involvement in HIF-1 activation. PG - 53-8 AB - 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 HIF-1 transactivation activity. Moreover, using a kinase assay and Western blot experiments, we showed that HIF-1alpha 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. FAU - Minet, E AU - Minet E AD - Laboratoire de Biochimie et Biologie Cellulaire, Facultes Universitaires de la Paix, 61 rue de Bruxelles, 5000, Namur, Belgium. emmanuel.minet@fundp.ac.be FAU - Arnould, T AU - Arnould T FAU - Michel, G AU - Michel G FAU - Roland, I AU - Roland I FAU - Mottet, D AU - Mottet D FAU - Raes, M AU - Raes M FAU - Remacle, J AU - Remacle J FAU - Michiels, C AU - Michiels C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (DNA-Binding Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Nuclear Proteins) RN - 0 (Transcription Factors) RN - 42HK56048U (Tyrosine) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Blotting, Western MH - Cell Hypoxia/*physiology MH - Cell Line MH - Cell Nucleus/enzymology MH - DNA-Binding Proteins/*metabolism MH - Endothelium, Vascular/cytology/enzymology MH - Enzyme Activation/drug effects MH - Enzyme Inhibitors/pharmacology MH - Flavonoids/pharmacology MH - Humans MH - Hypoxia-Inducible Factor 1 MH - Hypoxia-Inducible Factor 1, alpha Subunit MH - Microcirculation/cytology/enzymology MH - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism MH - Mitogen-Activated Protein Kinase 3 MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism MH - Nuclear Proteins/*metabolism MH - Phosphorylation MH - Precipitin Tests MH - Protein Structure, Tertiary MH - Transcription Factors/metabolism MH - Tyrosine/metabolism EDAT- 2000/02/23 09:00 MHDA- 2000/04/15 09:00 CRDT- 2000/02/23 09:00 PHST- 2000/02/23 09:00 [pubmed] PHST- 2000/04/15 09:00 [medline] PHST- 2000/02/23 09:00 [entrez] AID - S0014-5793(00)01181-9 [pii] AID - 10.1016/s0014-5793(00)01181-9 [doi] PST - ppublish SO - FEBS Lett. 2000 Feb 18;468(1):53-8. doi: 10.1016/s0014-5793(00)01181-9.