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Publication : ERK5 MAPK regulates embryonic angiogenesis and acts as a hypoxia-sensitive repressor of vascular endothelial growth factor expression.

First Author  Sohn SJ Year  2002
Journal  J Biol Chem Volume  277
Issue  45 Pages  43344-51
PubMed ID  12221099 Mgi Jnum  J:80044
Mgi Id  MGI:2429454 Doi  10.1074/jbc.M207573200
Citation  Sohn SJ, et al. (2002) ERK5 MAPK regulates embryonic angiogenesis and acts as a hypoxia-sensitive repressor of vascular endothelial growth factor expression. J Biol Chem 277(45):43344-51
abstractText  During angiogenesis, endothelial cells undergo proliferation, reorganization, and stabilization to establish a mature vascular network. This process is critical for establishing a functional circulatory system during development and contributes to the pathological process of tumor growth. Here we report that embryos deficient for the ERK5 MAPK die between embryonic days 10.5 and 11.5 with angiogenic failure and cardiovascular defects. We show that ERK5 deficiency leads to an increased expression of the vascular endothelial growth factor (VEGF), dysregulation of which has been shown to impede angiogenic remodeling and vascular stabilization. Our data also reveal that ERK5 negatively regulates transcription from the vegf locus during hypoxic responses. Importantly, ERK5 is required at an earlier developmental stage than p38alpha, and p38alpha does not compensate for ERK5 deficiency. These results demonstrate that ERK5 plays a specific role in the regulation of early angiogenesis.
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