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G‐protein coupled receptor kinases as modulators of G‐protein signalling
Author(s) -
Bünemann Moritz,
Hosey M. Marlene
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0005z.x
Subject(s) - g protein coupled receptor , g protein coupled receptor kinase , rhodopsin like receptors , heterotrimeric g protein , internalization , microbiology and biotechnology , biology , g protein , endocytic cycle , arrestin , phosphorylation , effector , receptor , signal transducing adaptor protein , signalling , desensitization (medicine) , signal transduction , endocytosis , biochemistry , agonist , metabotropic receptor
G‐protein coupled receptors (GPCRs) comprise one of the largest classes of signalling molecules. A wide diversity of activating ligands induce the active conformation of GPCRs and lead to signalling via heterotrimeric G‐proteins and downstream effectors. In addition, a complex series of reactions participate in the ‘turn‐off’ of GPCRs in both physiological and pharmacological settings. Some key players in the inactivation or ‘desensitization’ of GPCRs have been identified, whereas others remain the target of ongoing studies. G‐protein coupled receptor kinases (GRKs) specifically phosphorylate activated GPCRs and initiate homologous desensitization. Uncoupling proteins, such as members of the arrestin family, bind to the phosphorylated and activated GPCRs and cause desensitization by precluding further interactions of the GPCRs and G‐proteins. Adaptor proteins, including arrestins, and endocytic machinery participate in the internalization of GPCRs away from their normal signalling milieu. In this review we discuss the roles of these regulatory molecules as modulators of GPCR signalling.