Lysophosphatidic acid-induced c-fos up-regulation involves cyclic AMP response element-binding protein activated by mitogen- and stress-activated protein kinase-1

✍ Scribed by Chang-Wook Lee; Nam-Ho Kim; Ho-Kyew Choi; Yuanjie Sun; Ju-Suk Nam; Hae Jin Rhee; Jerold Chun; Sung-Oh Huh

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 215 KB
• Volume: 104
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21663

✦ Synopsis

Abstract

Lysophosphatidic acid (LPA) is a lipid growth factor that exerts diverse biological effects through its cognate receptor‐mediated signaling cascades. Recently, we reported that LPA stimulates cAMP response element‐binding protein (CREB) through mitogen‐ and stress‐activated protein kinase‐1 (MSK1). Previously, LPA has been shown to stimulate c‐fos mRNA expression in Rat‐2 fibroblast cells via a serum response element binding protein (SRF). However, involvement of CREB in LPA‐stimulated c‐fos gene expression is not elucidated yet. To investigate the CREB‐mediated c‐fos activation by LPA, various c‐fos promoter‐reporter constructs containing wild‐type and mutated SRE and CRE were tested for their inducibility by LPA in transient transfection assays. LPA‐stimulated c‐fos promoter activation was markedly decreased when SRE and CRE were mutated. A dominant negative CREB significantly down‐regulated the LPA‐stimulated c‐fos promoter activation. Chromatin immunoprecipitation assay revealed that LPA induced an increased binding of phosphorylated CREB and CREB‐binding protein (CBP) to the CRE region of the endogenous c‐fos promoter. Immunoblot analyses with various pharmacological inhibitors further showed that LPA induces up‐regulation of c‐fos mRNA level by activation of ERK, p38 MAPK, and MSK1. Taken together, our results suggest that CREB plays an important role in up‐regulation of c‐fos mRNA level in LPA‐stimulated Rat‐2 fibroblast cells. J. Cell. Biochem. 104: 785–794, 2008. © 2008 Wiley‐Liss, Inc.