Inherited diseases involving G proteins and G protein–coupled receptors

AM Spiegel, LS Weinstein - Annu. Rev. Med., 2004 - annualreviews.org
AM Spiegel, LS Weinstein
Annu. Rev. Med., 2004annualreviews.org
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 …
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 . 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.
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