ERK3 Promotes Endothelial Cell Functions by Upregulating SRC-3/SP1-mediated VEGFR2 Expression

Overview

Journal J Cell Physiol

Specialties Cell Biology
Physiology

Date 2014 Mar 4

PMID 24585635

Citations 26

Authors

Wei Wang

Ka Bian

Sreeram Vallabhaneni

Bin Zhang

Ray-Chang Wu

Bert W OMalley

Weiwen Long

Affiliations

Soon will be listed here.

Abstract

Despite a regain of interest recently in ERK3 kinase signaling, the molecular regulations of both ERK3 gene expression and protein kinase activity are still largely unknown. While it is shown that disruption of ERK3 gene causes neonatal lethality, cell type-specific functions of ERK3 signaling remain to be explored. In this study, we report that ERK3 gene expression is upregulated by cytokines through c-Jun in endothelial cells; c-Jun binds to the ERK3 gene and regulates its transcription. We further reveal a new role for ERK3 in regulating endothelial cell migration, proliferation and tube formation by upregulating SRC-3/SP-1-mediated VEGFR2 expression. The underlying molecular mechanism involves ERK3-stimulated formation of a transcriptional complex involving coactivator SRC-3, transcription factor SP-1 and the secondary coactivator CBP. Taken together, our study identified a molecular regulatory mechanism of ERK3 gene expression and revealed a previously unknown role of ERK3 in regulating endothelial cell functions.

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