Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2002 Nov 8;277(45):43344-51. Epub 2002 Sep 6.

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

Author information

  • 1Department of Molecular and Cell Biology, Division of Immunology and Cancer Research Laboratory, University of California, Berkeley, California 94720-3200, USA.

Abstract

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.

PMID:
12221099
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk