Constitutive activation of G protein-coupled receptors and diseases: insights into mechanisms of activation and therapeutics.

ABSTRACT: The existence of constitutive activity for G protein-coupled receptors (GPCRs) was first described in 1980s. In 1991, the first naturally occurring constitutively active mutations in GPCRs that cause diseases were reported in rhodopsin. Since then, numerous constitutively active mutations that cause human diseases were reported in several additional receptors. More recently, loss of constitutive activity was postulated to also cause diseases. Animal models expressing some of these mutants confirmed the roles of these mutations in the pathogenesis of the diseases. Detailed functional studies of these naturally occurring mutations, combined with homology modeling using rhodopsin crystal structure as the template, lead to important insights into the mechanism of activation in the absence of c

SUBMITTER: Tao YX 

PROVIDER: S-EPMC2668812 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature