Inherited diseases involving G proteins and G protein-coupled receptors

Allen M. Spiegel, Lee S. Weinstein

Research output: Contribution to journalReview article

181 Scopus citations

Abstract

Heterotrimeric G proteins couple seven-transmembrane receptors for diverse extracellular signals to effectors that generate intracellular signals altering cell function. Mutations in the gene encoding the α subunit of the G protein-coupling receptors to stimulation of adenylyl cyclase cause developmental abnormalities of bone, as well as hormone resistance (pseudohypoparathyroidism caused by loss-of-function mutations) and hormone hypersecretion (McCune-Albright syndrome caused by gain-of-function mutations). Loss- and gain-of-function mutations in genes encoding G protein-coupled receptors (GPCRs) have been identified as the cause of an increasing number of retinal, endocrine, metabolic, and developmental disorders. GPCRs comprise an evolutionarily conserved gene superfamily (1). By coupling to heterotrimeric G proteins, GPCRs transduce a wide variety of extracellular signals including monoamine, amino acid, and nucleoside neurotransmitters, as well as photons, chemical odorants, divalent cations, hormones, lipids, peptides and proteins. Following a brief overview of G protein-coupled signal transduction, we review the growing body of evidence that mutations in genes encoding GPCRs and G proteins are an important cause of human disease.

Original languageEnglish (US)
Pages (from-to)27-39
Number of pages13
JournalAnnual Review of Medicine
Volume55
DOIs
Publication statusPublished - Mar 19 2004
Externally publishedYes

    Fingerprint

Keywords

  • Gain- and loss-of-function mutations
  • Hormone resistance
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this