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Pathway Description
Gq Adrenergic Smooth Muscle Contraction
Bos taurus
Category:
Metabolite Pathway
Sub-Category:
Physiological
Created: 2023-09-01
Last Updated: 2023-11-27
Gq protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the Gq/11 (Gq/G11) family or Gq/11/14/15 family to include closely related family members. G alpha subunits may be referred to as Gq alpha, Gαq, or Gqα. Gq proteins couple to G protein-coupled receptors to activate beta-type phospholipase C (PLC-β) enzymes. PLC-β in turn hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to diacyl glycerol (DAG) and inositol trisphosphate (IP3). IP3 acts as a second messenger to release stored calcium into the cytoplasm, while DAG acts as a second messenger that activates protein kinase C (PKC). Depending on the Gα subunit involved in the complex, the most well-known G-proteins are qualified as Gi, Gs, or Gq. They signal through different pathways. Gq proteins rely on enzymes of the phospholipase C family (PLC), while Gs and Gi proteins respectively stimulate and inhibit adenylate cyclase (AC) and thus act upon the amount of cytosolic cAMP. Contraction of smooth muscle is initiated by a Ca2+-mediated change in the thick filaments, whereas in striated muscle Ca2+ mediates contraction by changes in the thin filaments. In response to specific stimuli in smooth muscle, the intracellular concentration of Ca2+ increases, and this activator Ca2+ combines with the acidic protein calmodulin. This complex activates MLC kinase to phosphorylate the light chain of myosin (Fig. 1). Cytosolic Ca2+ is increased through Ca2+ release from intracellular stores (sarcoplasmic reticulum) as well as entry from the extracellular space through Ca2+ channels (receptor-operated Ca2+ channels). Agonists (norepinephrine, angiotensin II, endothelin, etc.) binding to serpentine receptors, coupled to a heterotrimeric G protein, stimulate phospholipase C activity. This enzyme is specific for the membrane lipid phosphatidylinositol 4,5-bisphosphate to catalyze the formation of two potent second messengers: inositol trisphosphate (IP3) and diacylglycerol (DG). The binding of IP3 to receptors on the sarcoplasmic reticulum results in the release of Ca2+ into the cytosol. DG, along with Ca2+, activates protein kinase C (PKC), which phosphorylates specific target proteins. There are several isozymes of PKC in smooth muscle, and each has a tissue-specific role (e.g., vascular, uterine, intestinal, etc.). In many cases, PKC has contraction-promoting effects such as phosphorylation of L-type Ca2+ channels or other proteins that regulate cross-bridge cycling. Adrenergic receptors that use Gq protein signalling to contract smooth muscles include the alpha-1 receptors. The alpha-1 receptor agonist actions include Smooth muscle contraction, mydriasis, vasoconstriction in the skin, mucosa and abdominal viscera & sphincter contraction of the GI tract and urinary bladder.
References
Gq Adrenergic Smooth Muscle Contraction References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Billington CK, Penn RB: Signaling and regulation of G protein-coupled receptors in airway smooth muscle. Respir Res. 2003;4(1):2. Epub 2003 Mar 14.
Pubmed: 12648290
Perez, Dianne M. (2006). The adrenergic receptors in the 21st century. Totowa, New Jersey: Humana Press. pp. 54, 129–134.
Gilman AG: G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615-49. doi: 10.1146/annurev.bi.56.070187.003151.
Pubmed: 3113327
Elsik CG, Tellam RL, Worley KC, Gibbs RA, Muzny DM, Weinstock GM, Adelson DL, Eichler EE, Elnitski L, Guigo R, Hamernik DL, Kappes SM, Lewin HA, Lynn DJ, Nicholas FW, Reymond A, Rijnkels M, Skow LC, Zdobnov EM, Schook L, Womack J, Alioto T, Antonarakis SE, Astashyn A, Chapple CE, Chen HC, Chrast J, Camara F, Ermolaeva O, Henrichsen CN, Hlavina W, Kapustin Y, Kiryutin B, Kitts P, Kokocinski F, Landrum M, Maglott D, Pruitt K, Sapojnikov V, Searle SM, Solovyev V, Souvorov A, Ucla C, Wyss C, Anzola JM, Gerlach D, Elhaik E, Graur D, Reese JT, Edgar RC, McEwan JC, Payne GM, Raison JM, Junier T, Kriventseva EV, Eyras E, Plass M, Donthu R, Larkin DM, Reecy J, Yang MQ, Chen L, Cheng Z, Chitko-McKown CG, Liu GE, Matukumalli LK, Song J, Zhu B, Bradley DG, Brinkman FS, Lau LP, Whiteside MD, Walker A, Wheeler TT, Casey T, German JB, Lemay DG, Maqbool NJ, Molenaar AJ, Seo S, Stothard P, Baldwin CL, Baxter R, Brinkmeyer-Langford CL, Brown WC, Childers CP, Connelley T, Ellis SA, Fritz K, Glass EJ, Herzig CT, Iivanainen A, Lahmers KK, Bennett AK, Dickens CM, Gilbert JG, Hagen DE, Salih H, Aerts J, Caetano AR, Dalrymple B, Garcia JF, Gill CA, Hiendleder SG, Memili E, Spurlock D, Williams JL, Alexander L, Brownstein MJ, Guan L, Holt RA, Jones SJ, Marra MA, Moore R, Moore SS, Roberts A, Taniguchi M, Waterman RC, Chacko J, Chandrabose MM, Cree A, Dao MD, Dinh HH, Gabisi RA, Hines S, Hume J, Jhangiani SN, Joshi V, Kovar CL, Lewis LR, Liu YS, Lopez J, Morgan MB, Nguyen NB, Okwuonu GO, Ruiz SJ, Santibanez J, Wright RA, Buhay C, Ding Y, Dugan-Rocha S, Herdandez J, Holder M, Sabo A, Egan A, Goodell J, Wilczek-Boney K, Fowler GR, Hitchens ME, Lozado RJ, Moen C, Steffen D, Warren JT, Zhang J, Chiu R, Schein JE, Durbin KJ, Havlak P, Jiang H, Liu Y, Qin X, Ren Y, Shen Y, Song H, Bell SN, Davis C, Johnson AJ, Lee S, Nazareth LV, Patel BM, Pu LL, Vattathil S, Williams RL Jr, Curry S, Hamilton C, Sodergren E, Wheeler DA, Barris W, Bennett GL, Eggen A, Green RD, Harhay GP, Hobbs M, Jann O, Keele JW, Kent MP, Lien S, McKay SD, McWilliam S, Ratnakumar A, Schnabel RD, Smith T, Snelling WM, Sonstegard TS, Stone RT, Sugimoto Y, Takasuga A, Taylor JF, Van Tassell CP, Macneil MD, Abatepaulo AR, Abbey CA, Ahola V, Almeida IG, Amadio AF, Anatriello E, Bahadue SM, Biase FH, Boldt CR, Carroll JA, Carvalho WA, Cervelatti EP, Chacko E, Chapin JE, Cheng Y, Choi J, Colley AJ, de Campos TA, De Donato M, Santos IK, de Oliveira CJ, Deobald H, Devinoy E, Donohue KE, Dovc P, Eberlein A, Fitzsimmons CJ, Franzin AM, Garcia GR, Genini S, Gladney CJ, Grant JR, Greaser ML, Green JA, Hadsell DL, Hakimov HA, Halgren R, Harrow JL, Hart EA, Hastings N, Hernandez M, Hu ZL, Ingham A, Iso-Touru T, Jamis C, Jensen K, Kapetis D, Kerr T, Khalil SS, Khatib H, Kolbehdari D, Kumar CG, Kumar D, Leach R, Lee JC, Li C, Logan KM, Malinverni R, Marques E, Martin WF, Martins NF, Maruyama SR, Mazza R, McLean KL, Medrano JF, Moreno BT, More DD, Muntean CT, Nandakumar HP, Nogueira MF, Olsaker I, Pant SD, Panzitta F, Pastor RC, Poli MA, Poslusny N, Rachagani S, Ranganathan S, Razpet A, Riggs PK, Rincon G, Rodriguez-Osorio N, Rodriguez-Zas SL, Romero NE, Rosenwald A, Sando L, Schmutz SM, Shen L, Sherman L, Southey BR, Lutzow YS, Sweedler JV, Tammen I, Telugu BP, Urbanski JM, Utsunomiya YT, Verschoor CP, Waardenberg AJ, Wang Z, Ward R, Weikard R, Welsh TH Jr, White SN, Wilming LG, Wunderlich KR, Yang J, Zhao FQ: The genome sequence of taurine cattle: a window to ruminant biology and evolution. Science. 2009 Apr 24;324(5926):522-8. doi: 10.1126/science.1169588.
Pubmed: 19390049
Henry GD, Trayer IP, Brewer S, Levine BA: The widespread distribution of alpha-N-trimethylalanine as the N-terminal amino acid of light chains from vertebrate striated muscle myosins. Eur J Biochem. 1985 Apr 1;148(1):75-82. doi: 10.1111/j.1432-1033.1985.tb08809.x.
Pubmed: 3979397
Kobayashi H, Inoue A, Mikawa T, Kuwayama H, Hotta Y, Masaki T, Ebashi S: Isolation of cDNA for bovine stomach 155 kDa protein exhibiting myosin light chain kinase activity. J Biochem. 1992 Dec;112(6):786-91. doi: 10.1093/oxfordjournals.jbchem.a123976.
Pubmed: 1284247
Kohama K, Okagaki T, Hayakawa K, Lin Y, Ishikawa R, Shimmen T, Inoue A: A novel regulatory effect of myosin light chain kinase from smooth muscle on the ATP-dependent interaction between actin and myosin. Biochem Biophys Res Commun. 1992 May 15;184(3):1204-11. doi: 10.1016/s0006-291x(05)80010-5.
Pubmed: 1534225
Ye LH, Hayakawa K, Kishi H, Imamura M, Nakamura A, Okagaki T, Takagi T, Iwata A, Tanaka T, Kohama K: The structure and function of the actin-binding domain of myosin light chain kinase of smooth muscle. J Biol Chem. 1997 Dec 19;272(51):32182-9. doi: 10.1074/jbc.272.51.32182.
Pubmed: 9405419
Ishiwata H, Katsuma S, Kizaki K, Patel OV, Nakano H, Takahashi T, Imai K, Hirasawa A, Shiojima S, Ikawa H, Suzuki Y, Tsujimoto G, Izaike Y, Todoroki J, Hashizume K: Characterization of gene expression profiles in early bovine pregnancy using a custom cDNA microarray. Mol Reprod Dev. 2003 May;65(1):9-18. doi: 10.1002/mrd.10292.
Pubmed: 12658628
Watterson DM, Sharief F, Vanaman TC: The complete amino acid sequence of the Ca2+-dependent modulator protein (calmodulin) of bovine brain. J Biol Chem. 1980 Feb 10;255(3):962-75.
Pubmed: 7356670
Laub M, Steppuhn JA, Bluggel M, Immler D, Meyer HE, Jennissen HP: Modulation of calmodulin function by ubiquitin-calmodulin ligase and identification of the responsible ubiquitylation site in vertebrate calmodulin. Eur J Biochem. 1998 Jul 15;255(2):422-31. doi: 10.1046/j.1432-1327.1998.2550422.x.
Pubmed: 9716384
Nukada T, Tanabe T, Takahashi H, Noda M, Haga K, Haga T, Ichiyama A, Kanagawa K, Hiranaga M, Matsuo, et al.: Primary structure of the alpha-subunit of bovine adenylate cyclase-inhibiting G-protein deduced from the cDNA sequence. FEBS Lett. 1986 Mar 3;197(1-2):305-10. doi: 10.1016/0014-5793(86)80347-7.
Pubmed: 2419165
Michel T, Winslow JW, Smith JA, Seidman JG, Neer EJ: Molecular cloning and characterization of cDNA encoding the GTP-binding protein alpha i and identification of a related protein, alpha h. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7663-7. doi: 10.1073/pnas.83.20.7663.
Pubmed: 3094012
Petrovski S, Kury S, Myers CT, Anyane-Yeboa K, Cogne B, Bialer M, Xia F, Hemati P, Riviello J, Mehaffey M, Besnard T, Becraft E, Wadley A, Politi AR, Colombo S, Zhu X, Ren Z, Andrews I, Dudding-Byth T, Schneider AL, Wallace G, Rosen ABI, Schelley S, Enns GM, Corre P, Dalton J, Mercier S, Latypova X, Schmitt S, Guzman E, Moore C, Bier L, Heinzen EL, Karachunski P, Shur N, Grebe T, Basinger A, Nguyen JM, Bezieau S, Wierenga K, Bernstein JA, Scheffer IE, Rosenfeld JA, Mefford HC, Isidor B, Goldstein DB: Germline De Novo Mutations in GNB1 Cause Severe Neurodevelopmental Disability, Hypotonia, and Seizures. Am J Hum Genet. 2016 May 5;98(5):1001-1010. doi: 10.1016/j.ajhg.2016.03.011. Epub 2016 Apr 21.
Pubmed: 27108799
Steinrucke S, Lohmann K, Domingo A, Rolfs A, Baumer T, Spiegler J, Hartmann C, Munchau A: Novel GNB1 missense mutation in a patient with generalized dystonia, hypotonia, and intellectual disability. Neurol Genet. 2016 Sep 13;2(5):e106. doi: 10.1212/NXG.0000000000000106. eCollection 2016 Oct.
Pubmed: 27668284
Lohmann K, Masuho I, Patil DN, Baumann H, Hebert E, Steinrucke S, Trujillano D, Skamangas NK, Dobricic V, Huning I, Gillessen-Kaesbach G, Westenberger A, Savic-Pavicevic D, Munchau A, Oprea G, Klein C, Rolfs A, Martemyanov KA: Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans. Hum Mol Genet. 2017 Mar 15;26(6):1078-1086. doi: 10.1093/hmg/ddx018.
Pubmed: 28087732
Robishaw JD, Kalman VK, Moomaw CR, Slaughter CA: Existence of two gamma subunits of the G proteins in brain. J Biol Chem. 1989 Sep 25;264(27):15758-61.
Pubmed: 2506169
Gautam N, Baetscher M, Aebersold R, Simon MI: A G protein gamma subunit shares homology with ras proteins. Science. 1989 May 26;244(4907):971-4. doi: 10.1126/science.2499046.
Pubmed: 2499046
Wilcox MD, Schey KL, Busman M, Hildebrandt JD: Determination of the complete covalent structure of the gamma 2 subunit of bovine brain G proteins by mass spectrometry. Biochem Biophys Res Commun. 1995 Jul 17;212(2):367-74. doi: 10.1006/bbrc.1995.1979.
Pubmed: 7626050
Mattera R, Codina J, Crozat A, Kidd V, Woo SL, Birnbaumer L: Identification by molecular cloning of two forms of the alpha-subunit of the human liver stimulatory (GS) regulatory component of adenylyl cyclase. FEBS Lett. 1986 Sep 29;206(1):36-42. doi: 10.1016/0014-5793(86)81336-9.
Pubmed: 3093273
Harris BA: Complete cDNA sequence of a human stimulatory GTP-binding protein alpha subunit. Nucleic Acids Res. 1988 Apr 25;16(8):3585. doi: 10.1093/nar/16.8.3585.
Pubmed: 3131741
Kozasa T, Itoh H, Tsukamoto T, Kaziro Y: Isolation and characterization of the human Gs alpha gene. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2081-5. doi: 10.1073/pnas.85.7.2081.
Pubmed: 3127824
Yoo SH, Oh YS, Kang MK, Huh YH, So SH, Park HS, Park HY: Localization of three types of the inositol 1,4,5-trisphosphate receptor/Ca(2+) channel in the secretory granules and coupling with the Ca(2+) storage proteins chromogranins A and B. J Biol Chem. 2001 Dec 7;276(49):45806-12. doi: 10.1074/jbc.M107532200. Epub 2001 Oct 2.
Pubmed: 11584008
Marks AR, Tempst P, Chadwick CC, Riviere L, Fleischer S, Nadal-Ginard B: Smooth muscle and brain inositol 1,4,5-trisphosphate receptors are structurally and functionally similar. J Biol Chem. 1990 Dec 5;265(34):20719-22.
Pubmed: 2174422
Schlossmann J, Ammendola A, Ashman K, Zong X, Huber A, Neubauer G, Wang GX, Allescher HD, Korth M, Wilm M, Hofmann F, Ruth P: Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta. Nature. 2000 Mar 9;404(6774):197-201. doi: 10.1038/35004606.
Pubmed: 10724174
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0126882
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