G Protein-Coupled Receptor and RhoA-Stimulated Transcriptional Responses: Links to Inflammation, Differentiation, and Cell Proliferation

被引:96
作者
Yu, Olivia M. [1 ,2 ]
Brown, Joan Heller [1 ]
机构
[1] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
NF-KAPPA-B; PHOSPHOLIPASE-C-EPSILON; COLONIC EPITHELIAL-CELLS; HIPPO SIGNALING PATHWAY; SPHINGOSINE; 1-PHOSPHATE; GENE-EXPRESSION; KINASE-D; MRTF-A; ACTIVATED RECEPTORS; THROMBIN RECEPTOR;
D O I
10.1124/mol.115.097857
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The low molecular weight G protein RhoA (rat sarcoma virus homolog family member A) serves as a node for transducing signals through G protein-coupled receptors (GPCRs). Activation of RhoA occurs through coupling of G proteins, most prominently, G(12/13), to Rho guanine nucleotide exchange factors. The GPCR ligands that are most efficacious for RhoA activation include thrombin, lysophosphatidic acid, sphingosine-1-phosphate, and thromboxane A2. These ligands also stimulate proliferation, differentiation, and inflammation in a variety of cell and tissues types. The molecular events underlying these responses are the activation of transcription factors, transcriptional coactivators, and downstream gene programs. This review describes the pathways leading from GPCRs and RhoA to the regulation of activator protein-1, NF kappa B (nuclear factor kappa-light-chain-enhancer of activated B cells), myocardin-related transcription factor A, and Yes-associated protein. We also focus on the importance of two prominent downstream transcriptional gene targets, the inflammatory mediator cyclooxygenase 2, and the matricellular protein cysteine-rich angiogenic inducer 61 (CCN1). Finally, we describe the importance of GPCR-induced activation of these pathways in the pathophysiology of cancer, fibrosis, and cardiovascular disease.
引用
收藏
页码:171 / 180
页数:10
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