RT Journal Article
SR Electronic
T1 G Protein–Coupled Receptor and RhoA-Stimulated Transcriptional Responses: Links to Inflammation, Differentiation, and Cell Proliferation
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 171
OP 180
DO 10.1124/mol.115.097857
VO 88
IS 1
A1 Yu, Olivia M.
A1 Brown, Joan Heller
YR 2015
UL http://molpharm.aspetjournals.org/content/88/1/171.abstract
AB 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, G12/13, 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, NFκB (nuclear factor κ-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.