Constitutively signaling G-protein-coupled receptors and human disease

Dysregulation of G-protein-coupled receptor (GPCR) function has been shown 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), whereas another mutation causes the receptor to be in an active state in the absence of agonist ('gain of function' mutation), leading to 'constitutive 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, human herpesvirus provides a potential novel mechanism for viral tumorigenesis.