CONSTITUTIVELY SIGNALING G-PROTEIN-COUPLED RECEPTORS AND HUMAN-DISEASE

Dysregulation of G-protein-coupled receptor (GPCR) function has been s hown to be associated with a growing number of human diseases. In some diseases, mutation of an endogenous GPCR causes the receptor to lose the ability to bind agonist or signal ('loss of function' mutation), w hereas another mutation causes the receptor to be in an active state i n the absence of agonist ('gain of function' mutation), leading to 'co nstitutive signaling activity: A number of constitutively active GPCRs are tumorigenic in vitro and in animal models, and cause syndromes of hyperfunction and/or tumors in humans. The recent characterization of a constitutively active GPCR in the genome of a disease-associated, h uman herpesvirus provides a potential novel mechanism for viral tumori genesis.