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Gαs-Activating Mutations

A Cause of Acromegaly, Thyroid Adenomas, Fibrous Dysplasia, and the McCune-Albright Syndrome

  • Chapter
G Proteins, Receptors, and Disease

Part of the book series: Contemporary Endocrinology ((COE,volume 6))

Abstract

Gs was the first G protein to be purified and characterized biochemically in detail. It is expressed in all mammalian cells, and is highly conserved not only in all vertebrates, but also in invertebrates, such as Drosophila and Caenorhabditis elegans. Gs couples receptors for numerous peptide hormones and monoamines to stimulation of adenylyl cyclase. Although it is now clear that G-protein βγ-subunits can independently modulate adenylyl cyclase (positively or negatively depending on the adenylyl cyclase subtype), it is the Gαs-subunit that is the principal stimulator of adenylyl cyclase activity (1,2). Resultant cyclic adenosine monophosphate (cAMP) formation activates cAMP-dependent protein kinase A (PKA), causing phosphorylation of key intracellular proteins. Brief elevation in cAMP causes acute changes in cellular function; a more sustained increase in cAMP can lead to longer term alterations in cellular function, at least in part by modulating gene expression through cAMP-responsive transcription factors, such as cAMP response element binding protein (CREB). Not all of the actions of Gαs are necessarily mediated by cAMP activation of PKA. cAMP may act directly in certain cell types by regulating cyclic nucleotide-gated ion channels (3). There have also been suggestions that some actions of Gαs are independent of cAMP (4,5)

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Authors
  1. Allen M. Spiegel MD
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Editors and Affiliations

  1. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Allen M. Spiegel MD (Chief, Metabolic Diseases Branch) (Chief, Metabolic Diseases Branch)

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Spiegel, A.M. (1998). Gαs-Activating Mutations. In: Spiegel, A.M. (eds) G Proteins, Receptors, and Disease. Contemporary Endocrinology, vol 6. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-1802-9_3

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  • DOI: https://doi.org/10.1007/978-1-4612-1802-9_3

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4612-7290-8

  • Online ISBN: 978-1-4612-1802-9

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