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
|
Resource |
Human and Animal Cells |
A431(RCB0202) |