Integration of G-protein coupled receptor signaling pathways for activation of a transcription factor (EGR-3).
- Author:
Xuehai TAN
1
;
Pam SANDERS
;
Jack BOLADO
;
Mike WHITNEY
Author Information
1. Beijing Genomics Institute, Beijing 101300, China. tanxh@genomics.org.cn
- Publication Type:Journal Article
- MeSH:
Culture Media;
DNA-Binding Proteins;
metabolism;
Early Growth Response Protein 3;
Gene Expression Regulation;
Genes, Reporter;
Humans;
Jurkat Cells;
MAP Kinase Signaling System;
Receptors, CXCR4;
metabolism;
Receptors, G-Protein-Coupled;
metabolism;
Signal Transduction;
Transcription Factors;
metabolism;
beta-Lactamases;
metabolism
- From:
Genomics, Proteomics & Bioinformatics
2003;1(3):173-179
- CountryChina
- Language:English
-
Abstract:
We recently reported the use of a gene-trapping approach to isolate cell clones in which a reporter gene had integrated into genes modulated by T-cell activation. We have now tested a panel of clones from that report and identified the one that responds to a variety of G-protein coupled receptors (GPCR). The beta-lactamase tagged EGR-3 Jurkat cell was used to dissect specific GPCR signaling in vivo. Three GPCRs were studied, including the chemokine receptor CXCR4 (Gi-coupled) that was endogenously expressed, the platelet activation factor (PAF) receptor (Gq-coupled), and beta2 adrenergic receptor (Gs-coupled) that was both stably transfected. Agonists for each receptor activated transcription of the beta-lactamase tagged EGR-3 gene. Induction of EGR-3 through CXCR4 was blocked by pertussis toxin and PD58059, a specific inhibitor of MEK (MAPK/ERK kinase). Neither of these inhibitors blocked isoproterenol or PAF-mediated activation of EGR-3. Conversely, beta2- and PAF-mediated EGR-3 activation was blocked by the p38, specific inhibitor SB580. In addition, both beta2- and PAF-mediated EGR-3 activation could be synergistically activated by CXCR4 activation. This combined result indicates that EGR-3 can be activated through distinct signal transduction pathways by different GPCRs and that signals can be integrated and amplified to efficiently tune the level of activation.
