The Gs alpha subunit (Gαs, Gsα) is a subunit of the heterotrimeric G proteinGs that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. Gsα is a GTPase that functions as a cellular signaling protein. Gsα is the founding member of one of the four families of heterotrimeric G proteins, defined by the alpha subunits they contain: the Gαs family, Gαi/Gαo family, Gαq family, and Gα12/Gα13 family.[5] The Gs-family has only two members: the other member is Golf, named for its predominant expression in the olfactory system. In humans, Gsα is encoded by the GNAS complex locus, while Golfα is encoded by the GNAL gene.
Although each GTP-bound Gsα can activate only one adenylyl cyclase enzyme, amplification of the signal occurs because one receptor can activate multiple copies of Gs while that receptor remains bound to its activating agonist, and each Gsα-bound adenylyl cyclase enzyme can generate substantial cAMP to activate many copies of PKA.[8]
Receptorsedit
The G protein-coupled receptors that couple to the Gs family proteins include:
^ abcGRCh38: Ensembl release 89: ENSG00000087460 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000027523 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Ellis C, Nature Reviews Drug Discovery GPCR Questionnaire Participants (July 2004). "The state of GPCR research in 2004". Nature Reviews. Drug Discovery. 3 (7): 575, 577–626. doi:10.1038/nrd1458. PMID 15272499. S2CID 33620092.
^ abcdeGilman AG (1987). "G proteins: transducers of receptor-generated signals". Annual Review of Biochemistry. 56: 615–649. doi:10.1146/annurev.bi.56.070187.003151. PMID 3113327. S2CID 33992382.
^ abcdeRodbell M (1995). "Nobel Lecture: Signal transduction: Evolution of an idea". Bioscience Reports. 15 (3): 117–133. doi:10.1007/bf01207453. PMC1519115. PMID 7579038. S2CID 11025853.
^Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, White LE, eds. (2007). Neuroscience (4th ed.). New York: W. H. Freeman. p. 155. ISBN978-0-87893-697-7.
^Saroz, Yurii; Kho, Dan T.; Glass, Michelle; Graham, Euan Scott; Grimsey, Natasha Lillia (2019-10-19). "Cannabinoid Receptor 2 (CB 2 ) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes". ACS Pharmacology & Translational Science. 2 (6): 414–428. doi:10.1021/acsptsci.9b00049. ISSN 2575-9108. PMC7088898. PMID 32259074.
Overview of all the structural information available in the PDB for UniProt: P63092 (Guanine nucleotide-binding protein G(s) subunit alpha isoforms short) at the PDBe-KB.
alpha, subunit, alpha, subunit, gαs, gsα, subunit, heterotrimeric, protein, that, stimulates, camp, dependent, pathway, activating, adenylyl, cyclase, gsα, gtpase, that, functions, cellular, signaling, protein, gsα, founding, member, four, families, heterotrim. The Gs alpha subunit Gas Gsa is a subunit of the heterotrimeric G protein Gs that stimulates the cAMP dependent pathway by activating adenylyl cyclase Gsa is a GTPase that functions as a cellular signaling protein Gsa is the founding member of one of the four families of heterotrimeric G proteins defined by the alpha subunits they contain the Gas family Gai Gao family Gaq family and Ga12 Ga13 family 5 The Gs family has only two members the other member is Golf named for its predominant expression in the olfactory system In humans Gsa is encoded by the GNAS complex locus while Golfa is encoded by the GNAL gene GNASIdentifiersAliasesGNAS AHO C20orf45 GNAS1 GPSA GSA GSP NESP POH SCG6 SgVI GNAS complex locus PITA3External IDsOMIM 139320 MGI 95777 HomoloGene 55534 GeneCards GNASGene location Human Chr Chromosome 20 human 1 Band20q13 32Start58 839 718 bp 1 End58 911 192 bp 1 Gene location Mouse Chr Chromosome 2 mouse 2 Band2 H4 2 97 89 cMStart174 126 113 bp 2 End174 188 537 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inpostcentral gyrusBrodmann area 46pituitary glandanterior pituitaryBrodmann area 10entorhinal cortexsuperior frontal gyrusfrontal poleparotid glandleft lobe of thyroid glandTop expressed insuperior cervical ganglionentorhinal cortexdorsomedial hypothalamic nucleuspituitary glandmedian eminencedermissuperior colliculusleft lung lobeparaventricular nucleus of hypothalamusarcuate nucleusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionmolecular function nucleotide binding G protein beta gamma subunit complex binding GTP binding signal transducer activity metal ion binding protein binding GTPase activity guanyl nucleotide binding adenylate cyclase activator activity insulin like growth factor receptor binding mu type opioid receptor binding corticotropin releasing hormone receptor 1 binding beta 2 adrenergic receptor binding ionotropic glutamate receptor binding D1 dopamine receptor binding G protein coupled receptor bindingCellular componentcytoplasm perinuclear region of cytoplasm extracellular region transport vesicle cytoplasmic vesicle nucleus cytosol trans Golgi network membrane membrane plasma membrane heterotrimeric G protein complex intrinsic component of membrane extracellular exosome ruffle cell projection dendrite apical plasma membraneBiological processfemale pregnancy negative regulation of multicellular organism growth response to parathyroid hormone protein secretion positive regulation of cold induced thermogenesis hair follicle placode formation cellular response to catecholamine stimulus adenylate cyclase activating dopamine receptor signaling pathway adenylate cyclase activating G protein coupled receptor signaling pathway cognition regulation of insulin secretion cellular response to glucagon stimulus intracellular transport positive regulation of cAMP mediated signaling activation of adenylate cyclase activity cellular response to prostaglandin E stimulus adenylate cyclase activating adrenergic receptor signaling pathway sensory perception of smell positive regulation of GTPase activity developmental growth renal water homeostasis bone development platelet aggregation signal transduction G protein coupled receptor signaling pathway regulation of signal transduction skeletal system development genetic imprinting multicellular organism growth positive regulation of osteoclast differentiation endochondral ossification regulation of parathyroid hormone secretion post embryonic development post embryonic body morphogenesis DNA methylation cartilage development positive regulation of osteoblast differentiation tissue homeostasis sensory perception of chemical stimulus embryonic cranial skeleton morphogenesis energy reserve metabolic process skin development embryonic hindlimb morphogenesis adenylate cyclase modulating G protein coupled receptor signaling pathway positive regulation of catalytic activitySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez277814683EnsemblENSG00000087460ENSMUSG00000027523UniProtO95467P63092P84996Q5JWF2P63094Q6R0H7Q9Z0F1Q6R0H6RefSeq mRNA NM 000516NM 001077488NM 001077489NM 001077490NM 001309840NM 001309842NM 001309861NM 001309883NM 016592NM 080425NM 080426NM 001077507NM 001077510NM 010309NM 010310NM 019690NM 022000NM 201616NM 201617NM 201618NM 001310083NM 001310085NM 001364030RefSeq protein NP 000507NP 001070956NP 001070957NP 001070958NP 001296769NP 001296771NP 001296790NP 001296812NP 057676NP 536350NP 536351NP 000507 1NP 001070956 1NP 001070957 1NP 001070958 1NP 001296769 1NP 536350 2NP 536351 1NP 001070958 1NP 001296812 1NP 001296812 1NP 536350 2NP 001070975NP 001070978NP 001297012NP 001297014NP 034439NP 062664NP 068840NP 963910NP 963911NP 963912NP 001350959NP 001070975 1NP 001297014 1NP 034439 2NP 963911 1NP 062664 2NP 068840 2NP 001070975 1NP 001297014 1NP 963911 1NP 963912 1Location UCSC Chr 20 58 84 58 91 MbChr 2 174 13 174 19 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Receptors 3 See also 4 References 5 External linksFunction editMain article Heterotrimeric G protein The general function of Gs is to activate intracellular signaling pathways in response to activation of cell surface G protein coupled receptors GPCRs GPCRs function as part of a three component system of receptor transducer effector 6 7 The transducer in this system is a heterotrimeric G protein composed of three subunits a Ga protein such as Gsa and a complex of two tightly linked proteins called Gb and Gg in a Gbg complex 6 7 When not stimulated by a receptor Ga is bound to GDP and to Gbg to form the inactive G protein trimer 6 7 When the receptor binds an activating ligand outside the cell such as a hormone or neurotransmitter the activated receptor acts as a guanine nucleotide exchange factor to promote GDP release from and GTP binding to Ga which drives dissociation of GTP bound Ga from Gbg 6 7 In particular GTP bound activated Gsa binds to adenylyl cyclase to produce the second messenger cAMP which in turn activates the cAMP dependent protein kinase also called Protein Kinase A or PKA 6 7 Cellular effects of Gsa acting through PKA are described here Although each GTP bound Gsa can activate only one adenylyl cyclase enzyme amplification of the signal occurs because one receptor can activate multiple copies of Gs while that receptor remains bound to its activating agonist and each Gsa bound adenylyl cyclase enzyme can generate substantial cAMP to activate many copies of PKA 8 Receptors editThe G protein coupled receptors that couple to the Gs family proteins include 5 HT receptors types 5 HT4 and 5 HT7 ACTH receptor a k a MC2R Adenosine receptor types A2a and A2b Arginine vasopressin receptor 2 b adrenergic receptors types b1 b2 and b3 Calcitonin receptor Calcitonin gene related peptide receptor Cannabinoid receptor 2 9 Corticotropin releasing hormone receptor Dopamine receptors D1 like family D1 and D5 mainly through Golf in the striatum FSH receptor Gastric inhibitory polypeptide receptor Glucagon receptor Growth hormone releasing hormone receptor Histamine H2 receptor Luteinizing hormone choriogonadotropin receptor Melanocortin receptor MC1R MC2R a k a ACTH receptor MC3R MC4R MC5R Olfactory receptors through Golf in the olfactory neurons Parathyroid hormone receptor 1 Prostaglandin receptor types D2 and I2 Secretin receptor Thyrotropin receptor Trace amine associated receptor 1See also editSecond messenger system G protein coupled receptor Heterotrimeric G protein Adenylyl cyclase Protein kinase A Gi alpha subunit Gq alpha subunit G12 G13 alpha subunitsReferences edit a b c GRCh38 Ensembl release 89 ENSG00000087460 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000027523 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Ellis C Nature Reviews Drug Discovery GPCR Questionnaire Participants July 2004 The state of GPCR research in 2004 Nature Reviews Drug Discovery 3 7 575 577 626 doi 10 1038 nrd1458 PMID 15272499 S2CID 33620092 a b c d e Gilman AG 1987 G proteins transducers of receptor generated signals Annual Review of Biochemistry 56 615 649 doi 10 1146 annurev bi 56 070187 003151 PMID 3113327 S2CID 33992382 a b c d e Rodbell M 1995 Nobel Lecture Signal transduction Evolution of an idea Bioscience Reports 15 3 117 133 doi 10 1007 bf01207453 PMC 1519115 PMID 7579038 S2CID 11025853 Purves D Augustine GJ Fitzpatrick D Hall WC LaMantia AS White LE eds 2007 Neuroscience 4th ed New York W H Freeman p 155 ISBN 978 0 87893 697 7 Saroz Yurii Kho Dan T Glass Michelle Graham Euan Scott Grimsey Natasha Lillia 2019 10 19 Cannabinoid Receptor 2 CB 2 Signals via G alpha s and Induces IL 6 and IL 10 Cytokine Secretion in Human Primary Leukocytes ACS Pharmacology amp Translational Science 2 6 414 428 doi 10 1021 acsptsci 9b00049 ISSN 2575 9108 PMC 7088898 PMID 32259074 External links editG s alpha at the U S National Library of Medicine Medical Subject Headings MeSH GNAS protein human at the U S National Library of Medicine Medical Subject Headings MeSH Overview of all the structural information available in the PDB for UniProt P63092 Guanine nucleotide binding protein G s subunit alpha isoforms short at the PDBe KB Portal nbsp Biology Retrieved from https en wikipedia org w index php title Gs alpha subunit amp oldid 1181757805, wikipedia, wiki, book, books, library,
