gs gtp binding protein alpha subunits


Summary: A family of heterotrimeric GTP-binding protein alpha subunits that activate ADENYLYL CYCLASES.

Top Publications

  1. Kalinowski R, Berlot C, Jones T, Ross L, Jaffe L, Mehlmann L. Maintenance of meiotic prophase arrest in vertebrate oocytes by a Gs protein-mediated pathway. Dev Biol. 2004;267:1-13 pubmed
    ..Together with previous studies, these results support the conclusion that Gs-regulated generation of cAMP by the oocyte is a common mechanism for maintaining meiotic prophase arrest in vertebrate oocytes. ..
  2. Shi G, Jin L, Andres D. Pituitary adenylate cyclase-activating polypeptide 38-mediated Rin activation requires Src and contributes to the regulation of HSP27 signaling during neuronal differentiation. Mol Cell Biol. 2008;28:4940-51 pubmed publisher
  3. Palos Paz F, Perez Guerra O, Cameselle Teijeiro J, Rueda Chimeno C, Barreiro Morandeira F, Lado Abeal J, et al. Prevalence of mutations in TSHR, GNAS, PRKAR1A and RAS genes in a large series of toxic thyroid adenomas from Galicia, an iodine-deficient area in NW Spain. Eur J Endocrinol. 2008;159:623-31 pubmed publisher
    ..However, the genetic cause of TA was undetermined in 34% of the TA samples. ..
  4. Weinstein L, Xie T, Zhang Q, Chen M. Studies of the regulation and function of the Gs alpha gene Gnas using gene targeting technology. Pharmacol Ther. 2007;115:271-91 pubmed
    ..Our present knowledge gleaned from various Gnas gene targeting models are discussed in relation to the pathogenesis of human disorders with mutation or abnormal imprinting of the human orthologue GNAS. ..
  5. Kalfa N, Lumbroso S, Boulle N, Guiter J, Soustelle L, Costa P, et al. Activating mutations of Gsalpha in kidney cancer. J Urol. 2006;176:891-5 pubmed
    ..These findings suggest the implication of this pathway in human oncogenesis. It may provide a potential therapeutic approach to these frequent and aggressive tumors. ..
  6. Castellone M, Teramoto H, Williams B, Druey K, Gutkind J. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science. 2005;310:1504-10 pubmed
    ..These findings may provide a molecular framework for the future evaluation of chemopreventive strategies for colorectal cancer. ..
  7. Baragli A, Grieco M, Trieu P, Villeneuve L, Hebert T. Heterodimers of adenylyl cyclases 2 and 5 show enhanced functional responses in the presence of Galpha s. Cell Signal. 2008;20:480-92 pubmed publisher
  8. Plagge A, Kelsey G, Germain Lee E. Physiological functions of the imprinted Gnas locus and its protein variants Galpha(s) and XLalpha(s) in human and mouse. J Endocrinol. 2008;196:193-214 pubmed publisher
  9. Allen J, Yu J, Donati R, Rasenick M. Beta-adrenergic receptor stimulation promotes G alpha s internalization through lipid rafts: a study in living cells. Mol Pharmacol. 2005;67:1493-504 pubmed

More Information


  1. Mehlmann L, Jones T, Jaffe L. Meiotic arrest in the mouse follicle maintained by a Gs protein in the oocyte. Science. 2002;297:1343-5 pubmed
    ..This indicates that Gs activity in the oocyte is required to maintain meiotic arrest within the ovarian follicle and suggests that the follicle may keep the cell cycle arrested by activating Gs. ..
  2. Moravcova Z, Rudajev V, Stohr J, Novotny J, Cerny J, Parenti M, et al. Long-term agonist stimulation of IP prostanoid receptor depletes the cognate G(s)alpha protein in membrane domains but does not change the receptor level. Biochim Biophys Acta. 2004;1691:51-65 pubmed
    ..These data suggest a "supra-stoichiometric" arrangement of G proteins and corresponding receptors in DIMs. ..
  3. Abramowitz J, Grenet D, Birnbaumer M, Torres H, Birnbaumer L. XLalphas, the extra-long form of the alpha-subunit of the Gs G protein, is significantly longer than suspected, and so is its companion Alex. Proc Natl Acad Sci U S A. 2004;101:8366-71 pubmed
    ..XXLb proteins are likely to be found as stable dimers with AlexX. The N-terminally longer proteins may play regulatory roles. ..
  4. Bastepe M, Weinstein L, Ogata N, Kawaguchi H, Juppner H, Kronenberg H, et al. Stimulatory G protein directly regulates hypertrophic differentiation of growth plate cartilage in vivo. Proc Natl Acad Sci U S A. 2004;101:14794-9 pubmed
    ..These data suggest that Gsalpha is the primary mediator of the actions of PPR in growth plate chondrocytes and that there is haploinsufficiency of Gsalpha signaling in Gnas(+/E2-) chondrocytes. ..
  5. Plagge A, Gordon E, Dean W, Boiani R, Cinti S, Peters J, et al. The imprinted signaling protein XL alpha s is required for postnatal adaptation to feeding. Nat Genet. 2004;36:818-26 pubmed
    ..The opposing effects of maternally and paternally expressed products of the Gnas locus provide tangible molecular support for the parental-conflict hypothesis of imprinting. ..
  6. Hynes T, Mervine S, Yost E, Sabo J, Berlot C. Live cell imaging of Gs and the beta2-adrenergic receptor demonstrates that both alphas and beta1gamma7 internalize upon stimulation and exhibit similar trafficking patterns that differ from that of the beta2-adrenergic receptor. J Biol Chem. 2004;279:44101-12 pubmed
    ..Because Rab11 regulates traffic through recycling endosomes, co-localization of alphas and beta1gamma7 on these endosomes may indicate a means of recycling specific alphasbetagamma combinations to the plasma membrane. ..
  7. Weinstein L, Liu J, Sakamoto A, Xie T, Chen M. Minireview: GNAS: normal and abnormal functions. Endocrinology. 2004;145:5459-64 pubmed
    ..Mouse knockout models show that G(s)alpha and the alternative G(s)alpha isoform XLalphas that is expressed from the paternal GNAS allele may have opposite effects on energy metabolism in mice. ..
  8. Collins M, Sarlis N, Merino M, Monroe J, Crawford S, Krakoff J, et al. Thyroid carcinoma in the McCune-Albright syndrome: contributory role of activating Gs alpha mutations. J Clin Endocrinol Metab. 2003;88:4413-7 pubmed
    ..These findings suggest that the infrequent development of thyroid carcinoma in MAS patients involves additional mutational or epigenetic events...
  9. Fragoso M, Domenice S, Latronico A, Martin R, Pereira M, Zerbini M, et al. Cushing's syndrome secondary to adrenocorticotropin-independent macronodular adrenocortical hyperplasia due to activating mutations of GNAS1 gene. J Clin Endocrinol Metab. 2003;88:2147-51 pubmed
  10. Freson K, Jaeken J, Van Helvoirt M, de Zegher F, Wittevrongel C, Thys C, et al. Functional polymorphisms in the paternally expressed XLalphas and its cofactor ALEX decrease their mutual interaction and enhance receptor-mediated cAMP formation. Hum Mol Genet. 2003;12:1121-30 pubmed
    ..Both phenomena contribute to increased Gs signaling in patients with platelet hypersensitivity towards Gs-agonists and may be accompanied by neurological problems or growth deficiency. ..
  11. Puszyk W, Chatha K, Elsenheimer S, Crea F, Old R. Methylation of the imprinted GNAS1 gene in cell-free plasma DNA: equal steady-state quantities of methylated and unmethylated DNA in plasma. Clin Chim Acta. 2009;400:107-10 pubmed publisher
    ..Our data indicate that the methylation status of a DNA sequence has no effect on its steady state concentration in the cell-free DNA component of plasma, in healthy adults. ..
  12. Shnerb T, Lin N, Shurki A. What is the role of the helical domain of Gsalpha in the GTPase reaction?. Biochemistry. 2007;46:10875-85 pubmed
    ..The resemblance between the behavior of rasGAP and the HD suggests that the conclusion may be a general conclusion, applicable for all of the G-protein members. ..
  13. White C, Coetsee M, Morgan K, Flanagan C, Millar R, Lu Z. A crucial role for Galphaq/11, but not Galphai/o or Galphas, in gonadotropin-releasing hormone receptor-mediated cell growth inhibition. Mol Endocrinol. 2008;22:2520-30 pubmed publisher
  14. Kenakin T. Receptors as microprocessors: pharmacological nuance on metabotropic glutamate receptors 1alpha. Sci STKE. 2006;2006:pe29 pubmed
    ..Thus, ligands may not only turn receptors on and off, but may also select from their repertoire of signaling effects to further refine drug response. ..
  15. Orcel P, Chapurlat R. [Fibrous dysplasia of bone]. Rev Prat. 2007;57:1749-55 pubmed
    ..Tubular phosphate wasting is common and should be treated with phosphate supplement and calcitriol. The prognosis should improve with therapeutic advances, but this remains to be properly evaluated. ..
  16. Romo X, Pasten P, Martinez S, Soto X, Lara P, de Arellano A, et al. xRic-8 is a GEF for Gsalpha and participates in maintaining meiotic arrest in Xenopus laevis oocytes. J Cell Physiol. 2008;214:673-80 pubmed
    ..These results suggest that xRic-8 is participating in the immature oocyte by keeping Gsalpha-Gbetagamma-AC signaling complex in an activated state and therefore maintaining G2 arrest. ..
  17. Chen M, Feng H, Gupta D, Kelleher J, Dickerson K, Wang J, et al. G(s)alpha deficiency in skeletal muscle leads to reduced muscle mass, fiber-type switching, and glucose intolerance without insulin resistance or deficiency. Am J Physiol Cell Physiol. 2009;296:C930-40 pubmed publisher
    ..MGsKO mice are a valuable model for future studies of the role of G(s)alpha signaling pathways in skeletal muscle adaptation and their effects on whole body metabolism. ..
  18. Endo I, Matsumoto T, Fukumoto S. [Pathophysiology and classitication of parathyroidism]. Clin Calcium. 2007;17:1175-81 pubmed
    ..A new classification of hypoparathyroidism based upon these genetic abnormalities is proposed, and a diagnostic approach to patients with hypoparathyroidism is summarized. ..
  19. Eder S, Leierer J, Klimaschewski L, Wilhelm A, Volknandt W, Laslop A, et al. Secretion and molecular forms of NESP55, a novel genomically imprinted neuroendocrine-specific protein from AtT-20 cells. Neurosignals. 2004;13:298-307 pubmed
  20. Guan Y, Gao L, Ma H, Li Q, Zhang H, Yuan F, et al. Chronic intermittent hypobaric hypoxia decreases beta-adrenoceptor activity in right ventricular papillary muscle. Am J Physiol Heart Circ Physiol. 2010;298:H1267-72 pubmed publisher
    ..This mechanism may be involved in the cardiac protective effect of CIHH. ..
  21. Kim S, Kim J, Choi K, Ma S, Oh Y, Jung J, et al. Indomethacin enhances shuttling of aquaporin-2 despite decreased abundance in rat kidney. J Am Soc Nephrol. 2004;15:2998-3005 pubmed
    ..The generation of cAMP provoked by arginine vasopressin, sodium fluoride, or forskolin was blunted. These results suggest that indomethacin increases the shuttling of AQP2 while it decreases its abundance in the collecting duct. ..
  22. Lemos M, Harding B, Shalet S, Thakker R. A novel MEN1 intronic mutation associated with multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf). 2007;66:709-13 pubmed
    ..To investigate a family with an unusual combination of multiple endocrine neoplasia (MEN1) and the McCune-Albright syndrome for MEN1 mutations and activating GNAS1 mutations at codons Arg201 and Gln227...
  23. Lee C, Rivera R, Dubin A, Chun J. LPA(4)/GPR23 is a lysophosphatidic acid (LPA) receptor utilizing G(s)-, G(q)/G(i)-mediated calcium signaling and G(12/13)-mediated Rho activation. J Biol Chem. 2007;282:4310-7 pubmed
  24. Zhang L, Wu J, Ruan K. Solution structure of the first intracellular loop of prostacyclin receptor and implication of its interaction with the C-terminal segment of G alpha s protein. Biochemistry. 2006;45:1734-44 pubmed
    ..These data prompted intriguing speculations on the IP/G alpha s coupling which mediates vasodilatation and inhibition of platelet aggregation. ..
  25. Wilson C, McIntyre R, Arends M, Adams D. The activating mutation R201C in GNAS promotes intestinal tumourigenesis in Apc(Min/+) mice through activation of Wnt and ERK1/2 MAPK pathways. Oncogene. 2010;29:4567-75 pubmed publisher
    ..Our data strongly suggest that activating mutations of GNAS cooperate with inactivation of APC and are likely to contribute to colorectal tumourigenesis. ..
  26. Hutchinson D, Summers R, Gibbs M. Beta2- and beta3-adrenoceptors activate glucose uptake in chick astrocytes by distinct mechanisms: a mechanism for memory enhancement?. J Neurochem. 2007;103:997-1008 pubmed
    ..These results indicate that activation of beta2- and beta3-ARs causes glucose uptake in chick astrocytes by distinct mechanisms, which may be relevant for memory enhancement. ..
  27. Santiago F, Vieira R, Cordeiro M, Tellechea O, Figueiredo A. Unilateral progressive osseous heteroplasia. Eur J Dermatol. 2009;19:214-5 pubmed publisher
    ..Analysis of DNA showed no mutation of the GNAS gene. The clinical features were consistent with progressive osseous heteroplasia, atypically presented in a unilateral form, probably revealing a mosaic distribution. ..
  28. Palygin O, Pettus J, Shibata E. Regulation of caveolar cardiac sodium current by a single Gsalpha histidine residue. Am J Physiol Heart Circ Physiol. 2008;294:H1693-9 pubmed publisher
    ..We conclude that G(s)alpha H41 is a critical residue in the regulation of the increase in I(Na) in ventricular myocytes. ..
  29. Fereidoni M, Javan M, Semnanian S, Ahmadiani A. Chronic forced swim stress inhibits ultra-low dose morphine-induced hyperalgesia in rats. Behav Pharmacol. 2007;18:667-72 pubmed
    ..Finally, the interaction of stress with the G(alphas) signaling pathway may provide an explanation for the inhibitory effect of stress on development of tolerance to the analgesic effect of morphine. ..
  30. Amizuka N, Li M. [Parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor and the signal transduction]. Nihon Rinsho. 2005;63 Suppl 10:278-83 pubmed
  31. Riepe F, Ahrens W, Krone N, Fölster Holst R, Brasch J, Sippell W, et al. Early manifestation of calcinosis cutis in pseudohypoparathyroidism type Ia associated with a novel mutation in the GNAS gene. Eur J Endocrinol. 2005;152:515-9 pubmed
    ..The possibility of AHO and PHP Ia should be considered in children with hypothyroidism and calcinosis cutis. Systematic reviews regarding the frequency of calcinosis in AHO are warranted. ..
  32. Chan A, Wong Y. Gq-mediated activation of c-Jun N-terminal kinase by the gastrin-releasing peptide-preferring bombesin receptor is inhibited upon costimulation of the Gs-coupled dopamine D1 receptor in COS-7 cells. Mol Pharmacol. 2005;68:1354-64 pubmed
  33. Johnson Farley N, Kertesy S, Dubyak G, Cowen D. Enhanced activation of Akt and extracellular-regulated kinase pathways by simultaneous occupancy of Gq-coupled 5-HT2A receptors and Gs-coupled 5-HT7A receptors in PC12 cells. J Neurochem. 2005;92:72-82 pubmed
    ..Our finding of enhanced activation of neuroprotective Akt and ERK pathways by simultaneous occupancy of 5-HT2A and 5-HT7A receptors may also be relevant to the interaction of other neuronally expressed Gq- and Gs-coupled receptors. ..
  34. Hein P, Rochais F, Hoffmann C, Dorsch S, Nikolaev V, Engelhardt S, et al. Gs activation is time-limiting in initiating receptor-mediated signaling. J Biol Chem. 2006;281:33345-51 pubmed
    ..Taken together, our kinetic measurements demonstrate that the rate of G(S) activation limits initiation of G(S)-coupled receptor signaling. ..
  35. Hobson R, Hapiak V, Xiao H, Buehrer K, Komuniecki P, Komuniecki R. SER-7, a Caenorhabditis elegans 5-HT7-like receptor, is essential for the 5-HT stimulation of pharyngeal pumping and egg laying. Genetics. 2006;172:159-69 pubmed
    ..Taken together, these results suggest that SER-7 is essential for the 5-HT stimulation of both egg laying and pharyngeal pumping, but that other signaling pathways can probably fulfill similar roles in vivo. ..
  36. Almeida M, Latronico A. The molecular pathogenesis of childhood adrenocortical tumors. Horm Metab Res. 2007;39:461-6 pubmed
    ..Some of the molecular aspects of sporadic adrenocortical tumors arising in children and adolescents are reviewed here. ..
  37. Sheppard R. Vascular tone and the genomics of hypertension. Heart Fail Clin. 2010;6:45-53 pubmed publisher
    ..Future studies are needed to identify other potential genotypes that may influence therapeutic response in addition to clinical trials of specific medical therapy in individual patients based on specific genotypes. ..
  38. Malarkey C, Wang G, Ballicora M, MOTA DE FREITAS D. Evidence for two distinct Mg2+ binding sites in G(s alpha) and G(i alpha1) proteins. Biochem Biophys Res Commun. 2008;372:866-9 pubmed publisher
    ..Whereas the high affinity Mg(2+) site corresponds to that observed in published X-ray structures of G proteins, the low affinity Mg(2+) site may involve coordination to the terminal phosphate of the nucleotide. ..
  39. Kumagai K, Motomura K, Egashira M, Tomita M, Suzuki M, Uetani M, et al. A case of progressive osseous heteroplasia: a first case in Japan. Skeletal Radiol. 2008;37:563-7 pubmed publisher
    ..A nonsense mutation in exon 7 of the GNAS1 gene was identified in genomic DNA from the patient. No such case has been reported in East Asia or Japan before this patient. ..
  40. Stratakis C, Marx S. Multiple endocrine neoplasias in the era of translational medicine. Horm Metab Res. 2005;37:343-6 pubmed
  41. Norris R, Freudzon L, Freudzon M, Hand A, Mehlmann L, Jaffe L. A G(s)-linked receptor maintains meiotic arrest in mouse oocytes, but luteinizing hormone does not cause meiotic resumption by terminating receptor-G(s) signaling. Dev Biol. 2007;310:240-9 pubmed
    ..However, LH does not cause a change in Galpha(s) localization, indicating that LH does not act by terminating receptor-G(s) signaling. ..
  42. Terra S, Pauly D, Lee C, Patterson J, Adams K, Schofield R, et al. beta-Adrenergic receptor polymorphisms and responses during titration of metoprolol controlled release/extended release in heart failure. Clin Pharmacol Ther. 2005;77:127-37 pubmed
    ..Patients with the Gly389 variant and Ser49Ser genotype were significantly more likely to require increases in heart failure medications during beta-blocker titration and thus may require more frequent follow-up during titration. ..
  43. Strasser A, Wittmann H. Distinct interactions between the human adrenergic beta(2) receptor and Galpha(s)--an in silico study. J Mol Model. 2010;16:1307-18 pubmed publisher
    ..A mean number of about 14 hydrogen bonds was observed between the active receptor and Galpha(s) for both conformations. Based on these results, two energetically favored beta(2)-Galpha(s)complexes can be proposed. ..
  44. Sakamoto A, Weinstein L, Plagge A, Eckhaus M, Kelsey G. GNAS haploinsufficiency leads to subcutaneous tumor formation with collagen and elastin deposition and calcification. Endocr Res. 2009;34:1-9 pubmed publisher
    ..These findings provide in vivo evidence that G(s)alpha pathways inhibit fibroblast and endothelial proliferation and matrix deposition. ..
  45. Paris F, Philibert P, Lumbroso S, Servant N, Kalfa N, Sultan C. Isolated Cushing's syndrome: an unusual presentation of McCune-Albright syndrome in the neonatal period. Horm Res. 2009;72:315-9 pubmed publisher
    ..This female newborn later developed the classical triad of MAS, reinforcing this diagnosis. Cushing's syndrome in infants, even when isolated, may suggest a diagnosis of MAS. ..
  46. Most P, Seifert H, Gao E, Funakoshi H, Völkers M, Heierhorst J, et al. Cardiac S100A1 protein levels determine contractile performance and propensity toward heart failure after myocardial infarction. Circulation. 2006;114:1258-68 pubmed
  47. Chakrabarti S, Chang A, Gintzler A. Subcellular localization of mu-opioid receptor G(s) signaling. J Pharmacol Exp Ther. 2010;333:193-200 pubmed publisher
    ..MOR-stimulated trafficking of G(s)alpha and AC into caveolae and the likelihood of increased MOR G(s)alpha coupling within caveolae could suggest that they contain the downstream effectors for MOR G(s)alpha AC signaling. ..
  48. Kronenberg H. Gs signaling in osteoblasts and hematopoietic stem cells. Ann N Y Acad Sci. 2010;1192:327-9 pubmed publisher
  49. Wagoner H, Steinmetz R, Bethin K, Eugster E, Pescovitz O, Hannon T. GNAS mutation detection is related to disease severity in girls with McCune-Albright syndrome and precocious puberty. Pediatr Endocrinol Rev. 2007;4 Suppl 4:395-400 pubmed
    ..Until improvements in the diagnostic utility of GNAS activating mutation analysis from leukocyte genomic DNA occur, such testing in patients with atypical forms of MAS should continue to be reserved for research settings. ..
  50. Sargin H, Gozu H, Bircan R, Sargin M, Avsar M, Ekinci G, et al. A case of McCune-Albright syndrome associated with Gs alpha mutation in the bone tissue. Endocr J. 2006;53:35-44 pubmed
    ..We described a case of MAS associated with Gs alpha mutation in the bone tissue, presenting with polyostotic fibrous dysplasia, subclinical hyperthyroidism and acromegaly. ..
  51. Merlen C, Fabrega S, Desbuquois B, Unson C, Authier F. Glucagon-mediated internalization of serine-phosphorylated glucagon receptor and Gsalpha in rat liver. FEBS Lett. 2006;580:5697-704 pubmed
  52. Ngai J, Methi T, Andressen K, Levy F, Torgersen K, Vang T, et al. The heterotrimeric G-protein alpha-subunit Galphaq regulates TCR-mediated immune responses through an Lck-dependent pathway. Eur J Immunol. 2008;38:3208-18 pubmed publisher
    ..Together these data argue for a role of Galphaq in the fine-tuning of proximal TCR signals at the level of Lck and a negative regulatory role of Galphaq in transcriptional activation of cytokine responses. ..
  53. Ruiz M, Albasanz J, Leon D, Ros M, Andrés A, Martín M. Different modulation of inhibitory and stimulatory pathways mediated by adenosine after chronic in vivo agonist exposure. Brain Res. 2005;1031:211-21 pubmed