Abstract
The heterotrimeric G proteins transduce signals from hormone receptors to regulate effector molecules — enzymes and ion channels — which in turn generate intracellular messengers that alter cellular function. Each member of the growing G protein family participates in a cycle of GTP binding and hydrolysis that amplifies hormonal signals. Mutations that interfere with this cycle cause or contribute to the pathogenesis of several endocrine diseases: 1. Pseudohypoparathyroidism. type I. in which patients inherit a defective copy of the αs gene, which encodes the a subunit of Gs. the stimulatory regulator of adenylylcyclase. 2. Acromegaly. due in ∼40% of cases to somatic mutations in pituitary somatotrophs that constitutively activate αs and elevate cyclic AMP. 3. Tumors of thyroid, adrenal cortex, and ovarian granulosa cells, in which somatic mutations activate αs or the α subunit of a different G protein, G12. 4. McCune-Albright Syndrome, in which an activating αs mutation occurs in the early embryo, and eventually causes multiple endocrine tumors. In combination with the mutations found in these diseases, biochemical and molecular genetic analysis of α subunits have opened avenues to molecular understanding of the GTPase cycle, the 3-dimensional structure of G proteins, and signaling interactions of these proteins with receptors and effectors.
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Bourne, H. G PROTEINS IN TRANSMEMBRANE SIGNALING. Pediatr Res 33 (Suppl 5), S1 (1993). https://doi.org/10.1203/00006450-199305001-00004
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DOI: https://doi.org/10.1203/00006450-199305001-00004