RRC ID 76395
Author Suzuki Y, Ozawa Y, Murakami K, Miyazaki H.
Title Lysophosphatidic acid inhibits epidermal-growth-factor-induced Stat1 signaling in human epidermoid carcinoma A431 cells.
Journal Biochem Biophys Res Commun
Abstract Lysophosphatidic acid (LPA) is a lipid mediator which acts on its putative G protein-coupled receptor (GPCR). Recently, activation of signal transducers and activators of transcription (STATs) mediated by GPCR has been reported. In this study, we examined the effect of LPA on STAT activation using the electrophoretic mobility shift assays and the heterologous promoter analysis in human epidermoid carcinoma A431 cells. We found that LPA inhibited epidermal growth factor (EGF)-induced Stat1 activation in a concentration-dependent manner. Other phospholipase C (PLC)-coupled GPCR agonists, bradykinin and ATP, also inhibited Stat1 activation. This inhibitory effect of LPA was completely mimicked by an activator of protein kinase C (PKC), a PLC-downstream effector. These findings suggest that the inhibitory effect on EGF-induced Stat1 activation may be a general characteristic of PLC-coupled GPCRs and PKC pathway may be mainly associated with this inhibitory effect. This is the first evidence showing that GPCR agonists inhibit the Janus kinase-independent Stat1 activation induced by receptor tyrosine kinase.
Volume 240(3)
Pages 856-61
Published 1997-11-26
DOI 10.1006/bbrc.1997.7758
PII S0006-291X(97)97758-5
PMID 9398658
MeSH Bradykinin / pharmacology Carcinoma, Squamous Cell DNA-Binding Proteins / metabolism* Epidermal Growth Factor / antagonists & inhibitors* Epinephrine / pharmacology GTP-Binding Proteins / metabolism Genes, Reporter / genetics Humans Lysophospholipids / pharmacology* Nuclear Proteins / metabolism Oligodeoxyribonucleotides / chemistry Oligodeoxyribonucleotides / metabolism Promoter Regions, Genetic / genetics Protein Kinase C / metabolism Receptors, Cell Surface / metabolism Regulatory Sequences, Nucleic Acid STAT1 Transcription Factor Signal Transduction / drug effects* Tetradecanoylphorbol Acetate / pharmacology Trans-Activators / metabolism* Transcription, Genetic / drug effects Tumor Cells, Cultured Type C Phospholipases / metabolism
IF 2.985
Human and Animal Cells A431(RCB0202)