Molecular Biotechnology

, Volume 39, Issue 3, pp 239-264

First online:

Reviews in Molecular Biology and Biotechnology: Transmembrane Signaling by G Protein-Coupled Receptors

  • Louis M. LuttrellAffiliated withDivision of Endocrinology, Diabetes and Medical Genetics, Department of Medicine, Medical University of South CarolinaDepartment of Biochemistry & Molecular Biology, Medical University of South CarolinaThe Ralph H. Johnson Veterans Affairs Medical Center Email author 

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As the most diverse type of cell surface receptor, the importance heptahelical G protein-coupled receptors (GPCRs) to clinical medicine cannot be overestimated. Visual, olfactory and gustatory sensation, intermediary metabolism, cell growth and differentiation are all influenced by GPCR signals. The basic receptor-G protein-effector mechanism of GPCR signaling is tuned by a complex interplay of positive and negative regulatory events that amplify the effect of a hormone binding the receptor or that dampen cellular responsiveness. The association of heptahelical receptors with a variety of intracellular partners other than G proteins has led to the discovery of potential mechanisms of GPCR signaling that extend beyond the classical paradigms. While the physiologic relevance of many of these novel mechanisms of GPCR signaling remains to be established, their existence suggests that the mechanisms of GPCR signaling are even more diverse than previously imagined.


G protein-coupled receptors Heterotrimeric GTP-binding proteins Signal transduction Second messenger systems G protein-coupled receptor kinases Arrestins