Opioid signaling (Homo sapiens)

From WikiPathways

Revision as of 11:50, 1 November 2018 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
5, 31, 54474014, 15, 30, 4210381694723, 2927, 376, 18, 504422, 34, 5211, 412112, 492124, 472364426, 48439447558, 4513, 2520175328, 35471, 3, 4346477, 32, 4033endoplasmic reticulum lumennucleoplasmcytosolCAMK4 ADCY7 ITPR3 CALM1:4xCa2+ADCY2 PPP1CAADCY4 p-T34,S102,S137-PPP1R1B ADCY6 GNAI1 H2OATPp-T34,T75,S102,S137-PPP1R1B ADCY4 GNG5 POMC(237-267) GNGT1 GNB2 ADCY4 GDPGNG10 PDYN(226-230) GNAL PDYN(226-230) GNB5 p-T34,S137-PPP1R1B Calmodulin:CaMK IVCALM1 PPiADCY7 p-T34,T75,S137-PPP1R1B GNG7 GDP GNG11 GNGT2 p-S12,S13-CAMK4 GNAT3 GNAI1 p-T34,T75,S102,S137-PPP1R1B ADPp-T34-PPP1R1B GNG3 ADCY2 PRKACG H2OPhosphorylated (T34)DARPP-32:PP1APKA catalyticsubunitAHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerPRKACA GNG11 GNAL Galpha-olf:GDP:Adenylate cyclase (active) complexcAMP:PKA regulatorysubunitp-S102-PPP1R1B PDYN(226-230) GRK2GNAT3 GNAI1 ADCY2 ADCY1 Ca2+ PCCa2+ADCY2 ADCY6 GNG12 ADCY6 ADCY6 G-protein alpha(i):GTP:AdenylatecyclaseATPGNG11 GNAI3 CALM1:4xCa2+PRKACA GNG13 G protein alpha:GTPcomplexGNB3 GNAZ p-T34,T75,S102,S137-PPP1R1B PKA catalyticsubunitp-T34,S102-PPP1R1B ADCY9 GNGT2 GNB2 Fe3+ ADCY8 GNAZ GNAO1 GTPGNAI3 p-T34,T75,S137-PPP1R1B ADCY1 GNAI1 G protein alpha:GTPcomplexGNB3 GNAI3 GNAZ ADCY5 GNAI3 CAMK4 GNAL ADCY8 p-T34,S137-PPP1R1B GNB1 PLA2G4AGNB2 ADPp-T75,S102,S137-PPP1R1B GNG5 p-T34,S137-PPP1R1B PDE1B cAMPADCY6 (Gialpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)PPP1R1B phospho-CaMKIV:CalmodulinGNB1 Mn2+ GNG13 GTP GNAT2 POMC(237-267) PPP2R1A ADCY7 PiATPp-S102,S137-PPP1R1B ADCY3 ARAp-T34,T75,S102-PPP1R1B G-protein alpha(i/o/z/t) subunitPLCB3 PLC-betaGNG12 GRK2 CALM1 GTP GNAT2 GNAI1 Ca2+ PRKAR2B Opioid:MOR:Gprotein-GTP complexPLCB2 PDE1A GNAI2 p-T34-PPP1R1B GNG12 p-T34,T75-PPP1R1B phospho-CREB dimerGNB4 p-T34,T75,S137-PPP1R1B ADCY9 H2OGNAT3 PCATPDARPP-32phosphorylated onT34GNG5 PLCB2 GNAO1 GNG7 p-T34-PPP1R1B PPP3CA GNAT3 Mg2+ GNG2 Ca2+ GNAI3 PDYN(226-230) active PKC (alpha,gamma, delta)GNAI2 p-T75-DARPP32s:PRKACAZn2+ GNAI1 GNAT1 ATPGNAT2 GNG4 PLCB3 PLCB4 Galpha-olf:GTP:Adenylate cyclase (active) complexGNG10 H2OPRKACB ADCY4 ADCY3 Fe2+ Mg2+ DARPP-32 (and/orphosphorylated)GTPPPiITPR3 IP3 receptorhomotetramerGNGT2 ADCY3 GNB3 p-T34,S102,S137-PPP1R1B GDP GNG7 GNG5 OPRM1 activated PDE1C ADCY2 GNAI1 GNAI2 POMC(237-241) p-T75,S102-PPP1R1B GNB3 CDK5ADCY5 PP2B catalytic(Fe3+, Zn2+)ADCY7 p-T34,T75-PPP1R1B GNB5 p-T75-PPP1R1B ADCY1 ADCY8 PRKACA GNB1 GDP PDE4C GNAT1 PRKACG PDE4A GTP GNG13 GNB4 PRKCA p-T75,S102-PPP1R1B ADCY5 POMC(237-267) ADCY8 GNAT3 GDPPRKACB ATPactivated PDE1A ADCY4 ADCY8 ADCY4 PRKACB GNG2 ADCY3 p-S137-PPP1R1B ADCY5 PRKACB GNG2 OPRM1GNAI3 p-T75,S137-PPP1R1B GNAI1 ADCY7 GNB5 p-S29-ADRBK1p-S102,S137-PPP1R1B PP2A-ABdeltaCcomplexGNAO1 GTP ADCY5 GNG4 p-T34,T75-PPP1R1B PRKAR1B ADCY1 activated PDE1dimersCREB1p-T75,S102,S137-PPP1R1B GDP GNG8 GDP GNAI2 p-S133-CREB1ITPR1 ADCY3 GNG3 p-T75-DARPP32sPPP3R1 ADCY3 GNAL G alpha-olf:GDPcomplexPRKACB GNAT2 CALM1 GNAT1 GNAT3 ADCY5 GNB5 G-protein alpha:GDPPRKACAPDE4B GNAT1 p-T75,S137-PPP1R1B ADCY4 Ca2+GNAZ DARPP-32 (for CDK5phosphorylation)GNG11 ADPPC GTP ADCY7 GNAO1 POMC(237-241) adenosine5'-monophosphatePRKAR1B p-T75-PPP1R1B p-S137-PPP1R1B GTP GNAI2 PPP1R1B ADCY9 ITPR1 GNG8 GNAT2 GDP GTP Fe3+ (Gialpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)GNG2 ADCY2 ADCY9 GNAL ADCY1 ADCY7 Calmodulin:CaMK IVPDE1C GNG4 PPP3CB PRKACA ATPADCY9 p-S505,S727-PLA2G4A ADCY8 Ca2+ ADCY6 GNB1 ADCY3 p-T75-PPP1R1B GNAI2 PiPRKAR2A ADCY7 Ca2+ ADCY3 activated PDE1B Protein Kinase A,catalytic subunitscAMP G-protein alpha(i):GDPAdenylate cyclase(Mg2+ cofactor)GNAO1 ADPGNAL Opioid peptideGNAT3 GNAI2 GNG13 p-T185,Y187-MAPK1NAD+ PDE4D GNB1 POMC(237-241) GNAI1 GNAI2 adenosine5'-monophosphateGNAI1 GNB4 Activated PLC beta1/4GNAT3 ADCY7 p-S505,S727-PLA2G4AITPR2 PPP2CA PPP3CA GNAT2 Mg2+ Opioid:MOR:G-proteincomplexGNAZ GNAI2 I(1,4,5)P3GNG2 GNAO1 PKA tetramer:4xcAMPGNAT3 Opioid:MORp-T34,T75,S102-PPP1R1B ADCY8 GNAT3 PRKAR1A GNAO1 PRKACG ADPGNAI3 ADCY3 p-S54-PDE4BADCY1 GDP GNB4 CALM1 GNAI3 GNG10 PPP1CA GNAI3 (Gialpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)ITPR3 p-T75,S102-PPP1R1B PPP2CB PKA tetramerG alpha (i): GTPPPP3CA PPP3CA,B,C:Fe3+:Zn2+:4xCa2+:CaMGNAI1 PLCB1 PPP3 complexADCY5 Mg2+ GNAT3 GNAT3 GNAT2 Mg2+ p-T75,S102,S137-PPP1R1B p-T34,S102-PPP1R1B ADCY4 CALM1 GNG10 GNAI2 GNG8 GNAI2 GNAT1 GNG5 POMC(237-267) ATPADCY9 ITPR:I(1,4,5)P3tetramerMg2+ GNAI3 CAMK4PRKACG PLCB1 GNGT1 ADCY9 PPP3CB Adenylate cyclase(Mg2+ cofactor)GNG4 GNGT1 Ca2+ GNG4 Mg2+ G alpha-olf:GDPcomplexcAMPp-T75,S137-PPP1R1B ADCY8 p-S102-PPP1R1B GNB2 CALM1 GNG7 ITPR2 GNB3 PDYN(226-230) GTP GNAT1 PRKAR2B PPP3CC POMC(237-267) ITPR1 CALM1GNG13 OPRM1 GNAI2 PiH2OZn2+ OPRM1 POMC(237-241) PLCB4 PRKAR2B POMC(237-241) PRKACA ADCY6 ADCY5 DNA ITPR2 GNAI2 PRKACB GTP GNAI1 ADCY4 p-S133-CREB1 ADCY1 GNAT1 Mg2+ cAMP Zn2+ PPP3CC PPP2R5D I(1,4,5)P3 Opioid:MOR:Gprotein-GDP complexGDP GNAI3 GNAO1 GNB5 cAMPADPp-T34,T75,S102-PPP1R1B Fe3+ GNAI1 ADCY1 Mg2+ GNAT1 ADCY2 PRKAR2A ATPGNG10 GNGT2 PRKAR1A GNAI2 G-betagammaGNAT2 p-S133-CREB1GNG3 GNG8 ADCY1 PI(4,5)P2ADCY7 ADCY9 ADCY5 H2OPiGNAI3 GNAZ G alpha-olf:GTPGNGT1 ADCY9 PPP3CB Ca2+ GNAI2 ADCY2 PPP2R1B ADCY8 ADCY2 PRKACA ADCY3 PDE1 dimersGNG11 p-T34,T75,S102-PPP1R1B PRKACG p-T34,S102,S137-PPP1R1B ADCY1 GNGT1 PRKCG PRKCD 2-LysophosphatidylcholineGNG7 GNAZ p-T34,T75-PPP1R1B ADCY5 OPRM1 PRKACA GNAL PiGNAT1 ADPGRK2:calmodulinADCY9 PDE 4ADCY6 GNG12 GNAI3 DAGsCa2+ GNAL H2OGNG12 ADCY8 GTP CALM1 AHCYL1 ActivePLA2:phosphatidylcholineGNGT2 GNAT3 G-protein beta-gammacomplexCREB1p-T34,T75,S137-PPP1R1B GNAT2 GNB2 p-T34,S102-PPP1R1B GNG3 GNAI3 ADCY2 PRKAR1B CALM1 Adenylate cyclase(Mg2+ cofactor)Mg2+ PDE4BGNAO1 GNAT3 ADCY4 GNAI3 PRKAR2A GNAZ G protein-GDPcomplexADCY6 p-T34,T75,S102,S137-PPP1R1B GDP Ca2+ I(1,4,5)P3 GNAZ GNG8 ADCY6 Adenylate cyclase(Mg2+ cofactor)PRKACG PKA catalyticsubunitGNG3 GNB4 GNAT3 PRKAR1A GNAI1 GDP PPP3CC GNAI1 1951


Description

Opioids are chemical substances similar to opiates, the active substances found in opium (morphine, codeine etc.). Opioid action is mediated by the receptors for endogenous opioids; peptides such as the enkephalins, the endorphins or the dynorphins. Opioids possess powerful analgesic and sedative effects, and are widely used as pain-killers. Their main side-effect is the rapid establishment of a strong addiction. Opioids receptors are G-protein coupled receptors (GPCR). There are four classes of receptors: mu (MOR), kappa (KOR) and delta (DOR), and the nociceptin receptor (NOP). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 111885
Reactome-version 
Reactome version: 65
Reactome Author 
Reactome Author: Le Novere, Nicholas, Jassal, Bijay

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Bilbao A, Parkitna JR, Engblom D, Perreau-Lenz S, Sanchis-Segura C, Schneider M, Konopka W, Westphal M, Breen G, Desrivieres S, Klugmann M, Guindalini C, Vallada H, Laranjeira R, de Fonseca FR, Schumann G, Schütz G, Spanagel R.; ''Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine.''; PubMed Europe PMC Scholia
  2. Chatila T, Anderson KA, Ho N, Means AR.; ''A unique phosphorylation-dependent mechanism for the activation of Ca2+/calmodulin-dependent protein kinase type IV/GR.''; PubMed Europe PMC Scholia
  3. Huston E, Lumb S, Russell A, Catterall C, Ross AH, Steele MR, Bolger GB, Perry MJ, Owens RJ, Houslay MD.; ''Molecular cloning and transient expression in COS7 cells of a novel human PDE4B cAMP-specific phosphodiesterase, HSPDE4B3.''; PubMed Europe PMC Scholia
  4. Gonzalez GA, Montminy MR.; ''Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133.''; PubMed Europe PMC Scholia
  5. Vandeput F, Wolda SL, Krall J, Hambleton R, Uher L, McCaw KN, Radwanski PB, Florio V, Movsesian MA.; ''Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes.''; PubMed Europe PMC Scholia
  6. Li W, Yu ZX, Kotin RM.; ''Profiles of PrKX expression in developmental mouse embryo and human tissues.''; PubMed Europe PMC Scholia
  7. Ekholm D, Belfrage P, Manganiello V, Degerman E.; ''Protein kinase A-dependent activation of PDE4 (cAMP-specific cyclic nucleotide phosphodiesterase) in cultured bovine vascular smooth muscle cells.''; PubMed Europe PMC Scholia
  8. Börsch-Haubold AG, Bartoli F, Asselin J, Dudler T, Kramer RM, Apitz-Castro R, Watson SP, Gelb MH.; ''Identification of the phosphorylation sites of cytosolic phospholipase A2 in agonist-stimulated human platelets and HeLa cells.''; PubMed Europe PMC Scholia
  9. Yamamori E, Asai M, Yoshida M, Takano K, Itoi K, Oiso Y, Iwasaki Y.; ''Calcium/calmodulin kinase IV pathway is involved in the transcriptional regulation of the corticotropin-releasing hormone gene promoter in neuronal cells.''; PubMed Europe PMC Scholia
  10. Gu C, Cooper DM.; ''Calmodulin-binding sites on adenylyl cyclase type VIII.''; PubMed Europe PMC Scholia
  11. Oldham WM, Van Eps N, Preininger AM, Hubbell WL, Hamm HE.; ''Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins.''; PubMed Europe PMC Scholia
  12. Gerhardt MA, Neubig RR.; ''Multiple Gi protein subtypes regulate a single effector mechanism.''; PubMed Europe PMC Scholia
  13. Bibb JA, Snyder GL, Nishi A, Yan Z, Meijer L, Fienberg AA, Tsai LH, Kwon YT, Girault JA, Czernik AJ, Huganir RL, Hemmings HC, Nairn AC, Greengard P.; ''Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons.''; PubMed Europe PMC Scholia
  14. Evans JH, Spencer DM, Zweifach A, Leslie CC.; ''Intracellular calcium signals regulating cytosolic phospholipase A2 translocation to internal membranes.''; PubMed Europe PMC Scholia
  15. Goraya TA, Masada N, Ciruela A, Willoughby D, Clynes MA, Cooper DM.; ''Kinetic properties of Ca2+/calmodulin-dependent phosphodiesterase isoforms dictate intracellular cAMP dynamics in response to elevation of cytosolic Ca2+.''; PubMed Europe PMC Scholia
  16. Goraya TA, Masada N, Ciruela A, Cooper DM.; ''Sustained entry of Ca2+ is required to activate Ca2+-calmodulin-dependent phosphodiesterase 1A.''; PubMed Europe PMC Scholia
  17. Krasel C, Dammeier S, Winstel R, Brockmann J, Mischak H, Lohse MJ.; ''Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin.''; PubMed Europe PMC Scholia
  18. Dessauer CW, Gilman AG.; ''Purification and characterization of a soluble form of mammalian adenylyl cyclase.''; PubMed Europe PMC Scholia
  19. Reed KA, Tucker DE, Aloulou A, Adler D, Ghomashchi F, Gelb MH, Leslie CC, Oates JA, Boutaud O.; ''Functional characterization of mutations in inherited human cPLA₂ deficiency.''; PubMed Europe PMC Scholia
  20. Ahn JH, Sung JY, McAvoy T, Nishi A, Janssens V, Goris J, Greengard P, Nairn AC.; ''The B''/PR72 subunit mediates Ca2+-dependent dephosphorylation of DARPP-32 by protein phosphatase 2A.''; PubMed Europe PMC Scholia
  21. Taussig R, Tang WJ, Hepler JR, Gilman AG.; ''Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases.''; PubMed Europe PMC Scholia
  22. Li X, Li HP, Amsler K, Hyink D, Wilson PD, Burrow CR.; ''PRKX, a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and morphogenesis.''; PubMed Europe PMC Scholia
  23. Wall MA, Coleman DE, Lee E, Iñiguez-Lluhi JA, Posner BA, Gilman AG, Sprang SR.; ''The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2.''; PubMed Europe PMC Scholia
  24. Kleuss C, Raw AS, Lee E, Sprang SR, Gilman AG.; ''Mechanism of GTP hydrolysis by G-protein alpha subunits.''; PubMed Europe PMC Scholia
  25. Nishi A, Bibb JA, Matsuyama S, Hamada M, Higashi H, Nairn AC, Greengard P.; ''Regulation of DARPP-32 dephosphorylation at PKA- and Cdk5-sites by NMDA and AMPA receptors: distinct roles of calcineurin and protein phosphatase-2A.''; PubMed Europe PMC Scholia
  26. Taussig R, Iñiguez-Lluhi JA, Gilman AG.; ''Inhibition of adenylyl cyclase by Gi alpha.''; PubMed Europe PMC Scholia
  27. Wang JB, Johnson PS, Persico AM, Hawkins AL, Griffin CA, Uhl GR.; ''Human mu opiate receptor. cDNA and genomic clones, pharmacologic characterization and chromosomal assignment.''; PubMed Europe PMC Scholia
  28. Zigman JM, Westermark GT, LaMendola J, Boel E, Steiner DF.; ''Human G(olf) alpha: complementary deoxyribonucleic acid structure and expression in pancreatic islets and other tissues outside the olfactory neuroepithelium and central nervous system.''; PubMed Europe PMC Scholia
  29. Liang Z, Liu F, Grundke-Iqbal I, Iqbal K, Gong CX.; ''Down-regulation of cAMP-dependent protein kinase by over-activated calpain in Alzheimer disease brain.''; PubMed Europe PMC Scholia
  30. Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE.; ''The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells.''; PubMed Europe PMC Scholia
  31. James MA, Lu Y, Liu Y, Vikis HG, You M.; ''RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway.''; PubMed Europe PMC Scholia
  32. Lambright DG, Noel JP, Hamm HE, Sigler PB.; ''Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein.''; PubMed Europe PMC Scholia
  33. Sette C, Conti M.; ''Phosphorylation and activation of a cAMP-specific phosphodiesterase by the cAMP-dependent protein kinase. Involvement of serine 54 in the enzyme activation.''; PubMed Europe PMC Scholia
  34. Gullingsrud J, Kim C, Taylor SS, McCammon JA.; ''Dynamic binding of PKA regulatory subunit RI alpha.''; PubMed Europe PMC Scholia
  35. Di Pasquale G, Stacey SN.; ''Adeno-associated virus Rep78 protein interacts with protein kinase A and its homolog PRKX and inhibits CREB-dependent transcriptional activation.''; PubMed Europe PMC Scholia
  36. Saidak Z, Blake-Palmer K, Hay DL, Northup JK, Glass M.; ''Differential activation of G-proteins by mu-opioid receptor agonists.''; PubMed Europe PMC Scholia
  37. Walaas SI, Aswad DW, Greengard P.; ''A dopamine- and cyclic AMP-regulated phosphoprotein enriched in dopamine-innervated brain regions.''; PubMed Europe PMC Scholia
  38. Alt A, Clark MJ, Woods JH, Traynor JR.; ''Mu and Delta opioid receptors activate the same G proteins in human neuroblastoma SH-SY5Y cells.''; PubMed Europe PMC Scholia
  39. Hemmings HC, Williams KR, Konigsberg WH, Greengard P.; ''DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated neuronal phosphoprotein. I. Amino acid sequence around the phosphorylated threonine.''; PubMed Europe PMC Scholia
  40. Murakami M, Taketomi Y, Sato H, Yamamoto K.; ''Secreted phospholipase A2 revisited.''; PubMed Europe PMC Scholia
  41. Hemmings HC, Greengard P, Tung HY, Cohen P.; ''DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1.''; PubMed Europe PMC Scholia
  42. Lin LL, Wartmann M, Lin AY, Knopf JL, Seth A, Davis RJ.; ''cPLA2 is phosphorylated and activated by MAP kinase.''; PubMed Europe PMC Scholia
  43. Hamm HE.; ''The many faces of G protein signaling.''; PubMed Europe PMC Scholia
  44. Chuang TT, Paolucci L, De Blasi A.; ''Inhibition of G protein-coupled receptor kinase subtypes by Ca2+/calmodulin.''; PubMed Europe PMC Scholia
  45. Levay K, Satpaev DK, Pronin AN, Benovic JL, Slepak VZ.; ''Localization of the sites for Ca2+-binding proteins on G protein-coupled receptor kinases.''; PubMed Europe PMC Scholia
  46. Berstein G, Blank JL, Jhon DY, Exton JH, Rhee SG, Ross EM.; ''Phospholipase C-beta 1 is a GTPase-activating protein for Gq/11, its physiologic regulator.''; PubMed Europe PMC Scholia
  47. Schulz S, Mayer D, Pfeiffer M, Stumm R, Koch T, Höllt V.; ''Morphine induces terminal micro-opioid receptor desensitization by sustained phosphorylation of serine-375.''; PubMed Europe PMC Scholia
  48. Martin-Kleiner I, Balog T, Gabrilovac J.; ''Signal transduction induced by opioids in immune cells: a review.''; PubMed Europe PMC Scholia
  49. Régnauld KL, Leteurtre E, Gutkind SJ, Gespach CP, Emami S.; ''Activation of adenylyl cyclases, regulation of insulin status, and cell survival by G(alpha)olf in pancreatic beta-cells.''; PubMed Europe PMC Scholia
  50. Clark JD, Lin LL, Kriz RW, Ramesha CS, Sultzman LA, Lin AY, Milona N, Knopf JL.; ''A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP.''; PubMed Europe PMC Scholia
  51. Dessauer CW, Chen-Goodspeed M, Chen J.; ''Mechanism of Galpha i-mediated inhibition of type V adenylyl cyclase.''; PubMed Europe PMC Scholia
  52. King MM, Huang CY, Chock PB, Nairn AC, Hemmings HC, Chan KF, Greengard P.; ''Mammalian brain phosphoproteins as substrates for calcineurin.''; PubMed Europe PMC Scholia
  53. Caricasole A, Sala C, Roncarati R, Formenti E, Terstappen GC.; ''Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLC beta 1).''; PubMed Europe PMC Scholia
  54. Nagakura A, Takagi N, Takeo S.; ''Impairment of cerebral cAMP-mediated signal transduction system and of spatial memory function after microsphere embolism in rats.''; PubMed Europe PMC Scholia
  55. Standifer KM, Pasternak GW.; ''G proteins and opioid receptor-mediated signalling.''; PubMed Europe PMC Scholia
  56. Chen TY, Illing M, Molday LL, Hsu YT, Yau KW, Molday RS.; ''Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation.''; PubMed Europe PMC Scholia
  57. Ross D, Joyner WL.; ''Resting distribution and stimulated translocation of protein kinase C isoforms alpha, epsilon and zeta in response to bradykinin and TNF in human endothelial cells.''; PubMed Europe PMC Scholia
  58. Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, Sprang SR.; ''Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis.''; PubMed Europe PMC Scholia
  59. Johnson EA, Oldfield S, Braksator E, Gonzalez-Cuello A, Couch D, Hall KJ, Mundell SJ, Bailey CP, Kelly E, Henderson G.; ''Agonist-selective mechanisms of mu-opioid receptor desensitization in human embryonic kidney 293 cells.''; PubMed Europe PMC Scholia
  60. Burford NT, Tolbert LM, Sadee W.; ''Specific G protein activation and mu-opioid receptor internalization caused by morphine, DAMGO and endomorphin I.''; PubMed Europe PMC Scholia
  61. Simpson RE, Ciruela A, Cooper DM.; ''The role of calmodulin recruitment in Ca2+ stimulation of adenylyl cyclase type 8.''; PubMed Europe PMC Scholia
  62. Clark MJ, Traynor JR.; ''Mediation of adenylyl cyclase sensitization by PTX-insensitive GalphaoA, Galphai1, Galphai2 or Galphai3.''; PubMed Europe PMC Scholia
  63. Gaibelet G, Meilhoc E, Riond J, Saves I, Exner T, Liaubet L, Nürnberg B, Masson JM, Emorine LJ.; ''Nonselective coupling of the human mu-opioid receptor to multiple inhibitory G-protein isoforms.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
116415view09:08, 7 May 2021EweitzModified title
115086view17:03, 25 January 2021ReactomeTeamReactome version 75
113528view12:00, 2 November 2020ReactomeTeamReactome version 74
112726view16:12, 9 October 2020ReactomeTeamReactome version 73
101642view11:50, 1 November 2018ReactomeTeamreactome version 66
101178view21:37, 31 October 2018ReactomeTeamreactome version 65
100704view20:10, 31 October 2018ReactomeTeamreactome version 64
100254view16:55, 31 October 2018ReactomeTeamreactome version 63
99807view15:20, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99353view12:48, 31 October 2018ReactomeTeamreactome version 62
93848view13:40, 16 August 2017ReactomeTeamreactome version 61
93406view11:22, 9 August 2017ReactomeTeamreactome version 61
88062view14:04, 25 July 2016RyanmillerOntology Term : 'chemical compound signaling pathway' added !
88061view14:04, 25 July 2016RyanmillerOntology Term : 'signaling pathway' added !
86494view09:19, 11 July 2016ReactomeTeamreactome version 56
83304view10:42, 18 November 2015ReactomeTeamVersion54
81440view12:58, 21 August 2015ReactomeTeamVersion53
76919view08:19, 17 July 2014ReactomeTeamFixed remaining interactions
76624view11:59, 16 July 2014ReactomeTeamFixed remaining interactions
75955view10:01, 11 June 2014ReactomeTeamRe-fixing comment source
75657view10:55, 10 June 2014ReactomeTeamReactome 48 Update
75012view13:52, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74656view08:43, 30 April 2014ReactomeTeamReactome46
56299view16:38, 5 January 2013EgonwData typed a ChEBI metabolite as such.
42186view23:51, 4 March 2011MaintBotModified categories
42185view23:51, 4 March 2011MaintBot
42184view23:50, 4 March 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)ComplexR-HSA-170656 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)ComplexR-HSA-170659 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)ComplexR-HSA-170683 (Reactome)
2-LysophosphatidylcholineMetaboliteCHEBI:17504 (ChEBI)
ADCY1 ProteinQ08828 (Uniprot-TrEMBL)
ADCY2 ProteinQ08462 (Uniprot-TrEMBL)
ADCY3 ProteinO60266 (Uniprot-TrEMBL)
ADCY4 ProteinQ8NFM4 (Uniprot-TrEMBL)
ADCY5 ProteinO95622 (Uniprot-TrEMBL)
ADCY6 ProteinO43306 (Uniprot-TrEMBL)
ADCY7 ProteinP51828 (Uniprot-TrEMBL)
ADCY8 ProteinP40145 (Uniprot-TrEMBL)
ADCY9 ProteinO60503 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
AHCYL1 ProteinO43865 (Uniprot-TrEMBL)
AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerComplexR-HSA-5226920 (Reactome)
ARAMetaboliteCHEBI:15843 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated PLC beta 1/4ComplexR-HSA-111856 (Reactome)
Active PLA2:phosphatidylcholineComplexR-HSA-111860 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ComplexR-HSA-170665 (Reactome)
CALM1 ProteinP0DP23 (Uniprot-TrEMBL)
CALM1:4xCa2+ComplexR-HSA-194447 (Reactome)
CALM1:4xCa2+ComplexR-HSA-74294 (Reactome)
CALM1ProteinP0DP23 (Uniprot-TrEMBL)
CAMK4 ProteinQ16566 (Uniprot-TrEMBL)
CAMK4ProteinQ16566 (Uniprot-TrEMBL)
CDK5ProteinQ00535 (Uniprot-TrEMBL)
CREB1ProteinP16220 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Calmodulin:CaMK IVComplexR-HSA-111900 (Reactome)
Calmodulin:CaMK IVComplexR-HSA-112281 (Reactome)
DAGsMetaboliteCHEBI:18035 (ChEBI)
DARPP-32

phosphorylated on

T34
ComplexR-HSA-180075 (Reactome)
DARPP-32 (and/or phosphorylated)ComplexR-HSA-180056 (Reactome)
DARPP-32 (for CDK5 phosphorylation)ComplexR-HSA-180044 (Reactome)
DNA R-ALL-29428 (Reactome)
Fe2+ MetaboliteCHEBI:18248 (ChEBI)
Fe3+ MetaboliteCHEBI:29034 (ChEBI)
G alpha-olf:GDP:Adenylate cyclase (active) complexComplexR-HSA-170679 (Reactome)
G alpha-olf:GTP:Adenylate cyclase (active) complexComplexR-HSA-170655 (Reactome)
G alpha (i): GTPComplexR-HSA-392161 (Reactome)
G alpha-olf:GDP complexComplexR-HSA-170669 (Reactome)
G alpha-olf:GTPComplexR-HSA-170661 (Reactome)
G protein alpha:GTP complexComplexR-HSA-167438 (Reactome)
G protein-GDP complexComplexR-HSA-167418 (Reactome)
G-betagammaR-HSA-111865 (Reactome)
G-protein alpha (i):GDPComplexR-HSA-392164 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase
ComplexR-HSA-396910 (Reactome)
G-protein alpha (i/o/z/t) subunitComplexR-HSA-167413 (Reactome)
G-protein alpha:GDPComplexR-HSA-111864 (Reactome)
G-protein beta-gamma complexComplexR-HSA-167434 (Reactome)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GNAI1 ProteinP63096 (Uniprot-TrEMBL)
GNAI2 ProteinP04899 (Uniprot-TrEMBL)
GNAI3 ProteinP08754 (Uniprot-TrEMBL)
GNAL ProteinP38405 (Uniprot-TrEMBL)
GNAO1 ProteinP09471 (Uniprot-TrEMBL)
GNAT1 ProteinP11488 (Uniprot-TrEMBL)
GNAT2 ProteinP19087 (Uniprot-TrEMBL)
GNAT3 ProteinA8MTJ3 (Uniprot-TrEMBL)
GNAZ ProteinP19086 (Uniprot-TrEMBL)
GNB1 ProteinP62873 (Uniprot-TrEMBL)
GNB2 ProteinP62879 (Uniprot-TrEMBL)
GNB3 ProteinP16520 (Uniprot-TrEMBL)
GNB4 ProteinQ9HAV0 (Uniprot-TrEMBL)
GNB5 ProteinO14775 (Uniprot-TrEMBL)
GNG10 ProteinP50151 (Uniprot-TrEMBL)
GNG11 ProteinP61952 (Uniprot-TrEMBL)
GNG12 ProteinQ9UBI6 (Uniprot-TrEMBL)
GNG13 ProteinQ9P2W3 (Uniprot-TrEMBL)
GNG2 ProteinP59768 (Uniprot-TrEMBL)
GNG3 ProteinP63215 (Uniprot-TrEMBL)
GNG4 ProteinP50150 (Uniprot-TrEMBL)
GNG5 ProteinP63218 (Uniprot-TrEMBL)
GNG7 ProteinO60262 (Uniprot-TrEMBL)
GNG8 ProteinQ9UK08 (Uniprot-TrEMBL)
GNGT1 ProteinP63211 (Uniprot-TrEMBL)
GNGT2 ProteinO14610 (Uniprot-TrEMBL)
GRK2 ProteinP25098 (Uniprot-TrEMBL)
GRK2:calmodulinComplexR-HSA-111965 (Reactome)
GRK2ProteinP25098 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
I(1,4,5)P3 MetaboliteCHEBI:16595 (ChEBI)
I(1,4,5)P3MetaboliteCHEBI:16595 (ChEBI)
IP3 receptor homotetramerComplexR-HSA-169686 (Reactome)
ITPR1 ProteinQ14643 (Uniprot-TrEMBL)
ITPR2 ProteinQ14571 (Uniprot-TrEMBL)
ITPR3 ProteinQ14573 (Uniprot-TrEMBL)
ITPR:I(1,4,5)P3 tetramerComplexR-HSA-169696 (Reactome)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
Mn2+ MetaboliteCHEBI:29035 (ChEBI)
NAD+ MetaboliteCHEBI:15846 (ChEBI)
OPRM1 ProteinP35372 (Uniprot-TrEMBL)
OPRM1ProteinP35372 (Uniprot-TrEMBL)
Opioid peptideComplexR-HSA-167443 (Reactome)
Opioid:MOR:G protein-GDP complexComplexR-HSA-167403 (Reactome)
Opioid:MOR:G protein-GTP complexComplexR-HSA-167426 (Reactome)
Opioid:MOR:G-protein complexComplexR-HSA-167436 (Reactome)
Opioid:MORComplexR-HSA-112039 (Reactome)
PC MetaboliteCHEBI:16110 (ChEBI)
PCMetaboliteCHEBI:16110 (ChEBI)
PDE 4ComplexR-HSA-111960 (Reactome) cAMP selective hydrolase
PDE1 dimersComplexR-HSA-111952 (Reactome)
PDE1A ProteinP54750 (Uniprot-TrEMBL) Can hydrolyze both cAMP and cGMP
PDE1B ProteinQ01064 (Uniprot-TrEMBL) Can hydrolyze both cAMP and cGMP
PDE1C ProteinQ14123 (Uniprot-TrEMBL)
PDE4A ProteinP27815 (Uniprot-TrEMBL)
PDE4B ProteinQ07343 (Uniprot-TrEMBL)
PDE4BProteinQ07343 (Uniprot-TrEMBL)
PDE4C ProteinQ08493 (Uniprot-TrEMBL)
PDE4D ProteinQ08499 (Uniprot-TrEMBL)
PDYN(226-230) ProteinP01213 (Uniprot-TrEMBL)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PKA catalytic subunitComplexR-HSA-111920 (Reactome)
PKA tetramer:4xcAMPComplexR-HSA-8951729 (Reactome)
PKA tetramerComplexR-HSA-111922 (Reactome)
PLA2G4AProteinP47712 (Uniprot-TrEMBL)
PLC-betaComplexR-HSA-111854 (Reactome)
PLCB1 ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 ProteinQ00722 (Uniprot-TrEMBL)
PLCB3 ProteinQ01970 (Uniprot-TrEMBL)
PLCB4 ProteinQ15147 (Uniprot-TrEMBL)
POMC(237-241) ProteinP01189 (Uniprot-TrEMBL)
POMC(237-267) ProteinP01189 (Uniprot-TrEMBL)
PP2A-ABdeltaC complexComplexR-HSA-165961 (Reactome)
PP2B catalytic (Fe3+, Zn2+)ComplexR-HSA-201779 (Reactome)
PPP1CA ProteinP62136 (Uniprot-TrEMBL)
PPP1CAProteinP62136 (Uniprot-TrEMBL)
PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
PPP2CA ProteinP67775 (Uniprot-TrEMBL)
PPP2CB ProteinP62714 (Uniprot-TrEMBL)
PPP2R1A ProteinP30153 (Uniprot-TrEMBL)
PPP2R1B ProteinP30154 (Uniprot-TrEMBL)
PPP2R5D ProteinQ14738 (Uniprot-TrEMBL)
PPP3 complexComplexR-HSA-201788 (Reactome)
PPP3CA ProteinQ08209 (Uniprot-TrEMBL)
PPP3CA,B,C:Fe3+:Zn2+:4xCa2+:CaMComplexR-HSA-201762 (Reactome)
PPP3CB ProteinP16298 (Uniprot-TrEMBL)
PPP3CC ProteinP48454 (Uniprot-TrEMBL)
PPP3R1 ProteinP63098 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKACA ProteinP17612 (Uniprot-TrEMBL)
PRKACAProteinP17612 (Uniprot-TrEMBL)
PRKACB ProteinP22694 (Uniprot-TrEMBL)
PRKACG ProteinP22612 (Uniprot-TrEMBL)
PRKAR1A ProteinP10644 (Uniprot-TrEMBL)
PRKAR1B ProteinP31321 (Uniprot-TrEMBL)
PRKAR2A ProteinP13861 (Uniprot-TrEMBL)
PRKAR2B ProteinP31323 (Uniprot-TrEMBL)
PRKCA ProteinP17252 (Uniprot-TrEMBL)
PRKCD ProteinQ05655 (Uniprot-TrEMBL)
PRKCG ProteinP05129 (Uniprot-TrEMBL)
Phosphorylated (T34) DARPP-32:PP1AComplexR-HSA-180025 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)
Protein Kinase A, catalytic subunitsComplexR-HSA-111917 (Reactome)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
activated PDE1 dimersComplexR-HSA-9014905 (Reactome)
activated PDE1A ProteinP54750 (Uniprot-TrEMBL) Can hydrolyze both cAMP and cGMP
activated PDE1B ProteinQ01064 (Uniprot-TrEMBL) Can hydrolyze both cAMP and cGMP
activated PDE1C ProteinQ14123 (Uniprot-TrEMBL)
active PKC (alpha, gamma, delta)ComplexR-HSA-112002 (Reactome)
adenosine 5'-monophosphateMetaboliteCHEBI:16027 (ChEBI)
cAMP MetaboliteCHEBI:17489 (ChEBI)
cAMP:PKA regulatory subunitComplexR-HSA-111923 (Reactome)
cAMPMetaboliteCHEBI:17489 (ChEBI)
p-S102,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-S102-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-S12,S13-CAMK4 ProteinQ16566 (Uniprot-TrEMBL)
p-S133-CREB1 ProteinP16220 (Uniprot-TrEMBL)
p-S133-CREB1ProteinP16220 (Uniprot-TrEMBL)
p-S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-S29-ADRBK1ProteinP25098 (Uniprot-TrEMBL)
p-S505,S727-PLA2G4A ProteinP47712 (Uniprot-TrEMBL)
p-S505,S727-PLA2G4AProteinP47712 (Uniprot-TrEMBL)
p-S54-PDE4BProteinQ07343 (Uniprot-TrEMBL)
p-T185,Y187-MAPK1ProteinP28482 (Uniprot-TrEMBL)
p-T34,S102,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,S102-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75,S102,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75,S102-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75,S102,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75,S102-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75,S137-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75-DARPP32s:PRKACAComplexR-HSA-180050 (Reactome)
p-T75-DARPP32sComplexR-HSA-180026 (Reactome)
p-T75-PPP1R1B ProteinQ9UD71 (Uniprot-TrEMBL)
phospho-CREB dimerComplexR-HSA-111911 (Reactome)
phospho-CaMK IV:CalmodulinComplexR-HSA-111904 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)ArrowR-HSA-170686 (Reactome)
(Gi alpha1:GDP:Adenylate cyclase):(G alpha-olf:GDP)R-HSA-170674 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GDP)ArrowR-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)ArrowR-HSA-170671 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)R-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)R-HSA-170686 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)mim-catalysisR-HSA-170666 (Reactome)
(Gi alpha1:GTP:Adenylate cyclase):(G alpha-olf:GTP)mim-catalysisR-HSA-170686 (Reactome)
2-LysophosphatidylcholineArrowR-HSA-111883 (Reactome)
ADPArrowR-HSA-111898 (Reactome)
ADPArrowR-HSA-111912 (Reactome)
ADPArrowR-HSA-111915 (Reactome)
ADPArrowR-HSA-111919 (Reactome)
ADPArrowR-HSA-111970 (Reactome)
ADPArrowR-HSA-177275 (Reactome)
ADPArrowR-HSA-177284 (Reactome)
AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerTBarR-HSA-169683 (Reactome)
ARAArrowR-HSA-111883 (Reactome)
ATPR-HSA-111898 (Reactome)
ATPR-HSA-111912 (Reactome)
ATPR-HSA-111915 (Reactome)
ATPR-HSA-111919 (Reactome)
ATPR-HSA-111930 (Reactome)
ATPR-HSA-111970 (Reactome)
ATPR-HSA-170676 (Reactome)
ATPR-HSA-177275 (Reactome)
ATPR-HSA-177284 (Reactome)
Activated PLC beta 1/4ArrowR-HSA-111870 (Reactome)
Activated PLC beta 1/4R-HSA-112037 (Reactome)
Activated PLC beta 1/4mim-catalysisR-HSA-111879 (Reactome)
Active PLA2:phosphatidylcholineArrowR-HSA-111881 (Reactome)
Active PLA2:phosphatidylcholinemim-catalysisR-HSA-111883 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ArrowR-HSA-170674 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ArrowR-HSA-170677 (Reactome)
Adenylate cyclase (Mg2+ cofactor)R-HSA-170672 (Reactome)
Adenylate cyclase (Mg2+ cofactor)R-HSA-392206 (Reactome)
Adenylate cyclase (Mg2+ cofactor)mim-catalysisR-HSA-111930 (Reactome)
Adenylate cyclase (Mg2+ cofactor)mim-catalysisR-HSA-170672 (Reactome)
CALM1:4xCa2+ArrowR-HSA-111930 (Reactome)
CALM1:4xCa2+ArrowR-HSA-111956 (Reactome)
CALM1:4xCa2+ArrowR-HSA-74448 (Reactome)
CALM1:4xCa2+R-HSA-111913 (Reactome)
CALM1:4xCa2+R-HSA-201783 (Reactome)
CALM1R-HSA-111966 (Reactome)
CALM1R-HSA-74448 (Reactome)
CAMK4R-HSA-111913 (Reactome)
CDK5mim-catalysisR-HSA-180047 (Reactome)
CREB1R-HSA-111912 (Reactome)
CREB1R-HSA-111919 (Reactome)
Ca2+ArrowR-HSA-169683 (Reactome)
Ca2+R-HSA-111881 (Reactome)
Ca2+R-HSA-169683 (Reactome)
Ca2+R-HSA-74448 (Reactome)
Calmodulin:CaMK IVArrowR-HSA-111913 (Reactome)
Calmodulin:CaMK IVArrowR-HSA-112282 (Reactome)
Calmodulin:CaMK IVR-HSA-111915 (Reactome)
Calmodulin:CaMK IVR-HSA-112282 (Reactome)
Calmodulin:CaMK IVmim-catalysisR-HSA-111915 (Reactome)
DAGsArrowR-HSA-111879 (Reactome)
DARPP-32

phosphorylated on

T34
ArrowR-HSA-177275 (Reactome)
DARPP-32

phosphorylated on

T34
R-HSA-180038 (Reactome)
DARPP-32

phosphorylated on

T34
R-HSA-201787 (Reactome)
DARPP-32 (and/or phosphorylated)ArrowR-HSA-201787 (Reactome)
DARPP-32 (and/or phosphorylated)R-HSA-177275 (Reactome)
DARPP-32 (for CDK5 phosphorylation)ArrowR-HSA-201790 (Reactome)
DARPP-32 (for CDK5 phosphorylation)R-HSA-180047 (Reactome)
G alpha-olf:GDP:Adenylate cyclase (active) complexArrowR-HSA-170685 (Reactome)
G alpha-olf:GDP:Adenylate cyclase (active) complexR-HSA-170677 (Reactome)
G alpha-olf:GTP:Adenylate cyclase (active) complexArrowR-HSA-170672 (Reactome)
G alpha-olf:GTP:Adenylate cyclase (active) complexR-HSA-170685 (Reactome)
G alpha-olf:GTP:Adenylate cyclase (active) complexmim-catalysisR-HSA-170676 (Reactome)
G alpha-olf:GTP:Adenylate cyclase (active) complexmim-catalysisR-HSA-170685 (Reactome)
G alpha (i): GTPR-HSA-392206 (Reactome)
G alpha-olf:GDP complexArrowR-HSA-170674 (Reactome)
G alpha-olf:GDP complexArrowR-HSA-170677 (Reactome)
G alpha-olf:GTPR-HSA-170671 (Reactome)
G alpha-olf:GTPR-HSA-170672 (Reactome)
G protein alpha:GTP complexArrowR-HSA-112271 (Reactome)
G protein alpha:GTP complexR-HSA-111870 (Reactome)
G protein alpha:GTP complexR-HSA-167415 (Reactome)
G protein-GDP complexArrowR-HSA-167433 (Reactome)
G protein-GDP complexR-HSA-167408 (Reactome)
G-betagammaTBarR-HSA-111930 (Reactome)
G-protein alpha (i):GDPArrowR-HSA-170674 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase
ArrowR-HSA-392206 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase
R-HSA-170671 (Reactome)
G-protein alpha (i/o/z/t) subunitmim-catalysisR-HSA-167415 (Reactome)
G-protein alpha (i/o/z/t) subunitmim-catalysisR-HSA-167429 (Reactome)
G-protein alpha:GDPArrowR-HSA-112037 (Reactome)
G-protein alpha:GDPArrowR-HSA-167415 (Reactome)
G-protein alpha:GDPR-HSA-167433 (Reactome)
G-protein beta-gamma complexArrowR-HSA-112271 (Reactome)
G-protein beta-gamma complexR-HSA-167433 (Reactome)
GDPArrowR-HSA-167419 (Reactome)
GDPR-HSA-167415 (Reactome)
GRK2:calmodulinArrowR-HSA-111966 (Reactome)
GRK2R-HSA-111966 (Reactome)
GRK2R-HSA-111970 (Reactome)
GTPArrowR-HSA-167415 (Reactome)
GTPR-HSA-167429 (Reactome)
H2OR-HSA-111879 (Reactome)
H2OR-HSA-111883 (Reactome)
H2OR-HSA-111955 (Reactome)
H2OR-HSA-111962 (Reactome)
H2OR-HSA-112037 (Reactome)
H2OR-HSA-201787 (Reactome)
H2OR-HSA-201790 (Reactome)
I(1,4,5)P3ArrowR-HSA-111879 (Reactome)
I(1,4,5)P3ArrowR-HSA-169683 (Reactome)
I(1,4,5)P3R-HSA-169680 (Reactome)
IP3 receptor homotetramerR-HSA-169680 (Reactome)
ITPR:I(1,4,5)P3 tetramerArrowR-HSA-169680 (Reactome)
ITPR:I(1,4,5)P3 tetramermim-catalysisR-HSA-169683 (Reactome)
OPRM1ArrowR-HSA-167427 (Reactome)
OPRM1R-HSA-112042 (Reactome)
Opioid peptideArrowR-HSA-167427 (Reactome)
Opioid peptideR-HSA-112042 (Reactome)
Opioid:MOR:G protein-GDP complexArrowR-HSA-167408 (Reactome)
Opioid:MOR:G protein-GDP complexR-HSA-167419 (Reactome)
Opioid:MOR:G protein-GTP complexArrowR-HSA-167429 (Reactome)
Opioid:MOR:G protein-GTP complexR-HSA-112271 (Reactome)
Opioid:MOR:G-protein complexArrowR-HSA-167419 (Reactome)
Opioid:MOR:G-protein complexR-HSA-167429 (Reactome)
Opioid:MORArrowR-HSA-112042 (Reactome)
Opioid:MORArrowR-HSA-112271 (Reactome)
Opioid:MORR-HSA-167408 (Reactome)
Opioid:MORR-HSA-167427 (Reactome)
Opioid:MORmim-catalysisR-HSA-167408 (Reactome)
PCR-HSA-111881 (Reactome)
PCR-HSA-111883 (Reactome)
PDE 4mim-catalysisR-HSA-111962 (Reactome)
PDE1 dimersR-HSA-111956 (Reactome)
PDE4BR-HSA-177284 (Reactome)
PI(4,5)P2R-HSA-111879 (Reactome)
PKA catalytic subunitArrowR-HSA-111925 (Reactome)
PKA catalytic subunitR-HSA-111924 (Reactome)
PKA catalytic subunitmim-catalysisR-HSA-177275 (Reactome)
PKA catalytic subunitmim-catalysisR-HSA-177284 (Reactome)
PKA tetramer:4xcAMPArrowR-HSA-8951727 (Reactome)
PKA tetramer:4xcAMPR-HSA-111925 (Reactome)
PKA tetramerR-HSA-8951727 (Reactome)
PLA2G4AR-HSA-111898 (Reactome)
PLC-betaArrowR-HSA-112037 (Reactome)
PLC-betaR-HSA-111870 (Reactome)
PP2A-ABdeltaC complexmim-catalysisR-HSA-201790 (Reactome)
PP2B catalytic (Fe3+, Zn2+)R-HSA-201783 (Reactome)
PPP1CAR-HSA-180038 (Reactome)
PPP3 complexmim-catalysisR-HSA-201787 (Reactome)
PPP3CA,B,C:Fe3+:Zn2+:4xCa2+:CaMArrowR-HSA-201783 (Reactome)
PPiArrowR-HSA-111930 (Reactome)
PPiArrowR-HSA-170676 (Reactome)
PRKACAR-HSA-180073 (Reactome)
Phosphorylated (T34) DARPP-32:PP1AArrowR-HSA-180038 (Reactome)
Phosphorylated (T34) DARPP-32:PP1Amim-catalysisR-HSA-180038 (Reactome)
PiArrowR-HSA-112037 (Reactome)
PiArrowR-HSA-170666 (Reactome)
PiArrowR-HSA-170685 (Reactome)
PiArrowR-HSA-170686 (Reactome)
PiArrowR-HSA-201787 (Reactome)
PiArrowR-HSA-201790 (Reactome)
Protein Kinase A, catalytic subunitsArrowR-HSA-111924 (Reactome)
Protein Kinase A, catalytic subunitsmim-catalysisR-HSA-111919 (Reactome)
R-HSA-111870 (Reactome) The active form of G protein alpha subunit q (Gq-alpha) was found to activate phospholipase C beta-1 (PLC-beta1), in investigations using bovine membranes. Subsequently, all 4 human isoforms have been shown to be activated by Gq, though activation of PLCbeta-4 is limited. In recombinant assays, several activated rat G alpha q family members were found to stimulate human PLC-beta isoforms with the same rank order of decreasing potency. PLC-beta1 stimulation was slightly more than for PLC-beta3; PLC-beta3 stimulation was 10-fold greater than for beta-2. PLC-beta2 is expressed specifically in hematopoietic cells. PLC-beta acts directly on Gq to accelerate hydrolysis of bound GTP, thus PLC-betas are GTPase activating proteins (GAPs). The crystal structure of the C-terminal region from Turkey PLC-beta, revealed a novel fold composed almost entirely of three long helices forming a coiled-coil that dimerizes along its long axis in an antiparallel orientation. The extent of the dimer interface and gel exclusion chromatography data suggest that PLC-betas are functionally dimeric.
R-HSA-111879 (Reactome) The phospholipase C (PLC) family of enzymes is both diverse and complex. The isoforms beta, gamma and delta (each have subtypes) make up the members of this family. One type, PLC-beta1, hydrolyzes phosphatidylinositol bisphosphate (PIP2) into two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular calcium stores while DAG activates protein kinase C isoforms which are involved in regulatory functions.
R-HSA-111881 (Reactome) The 85kDa cytosolic phospholipase A2 (cPLA2 - PLA2G4A) is involved in cell signalling processes and inflammatory response and is regulated by phosphorylation and calcium concentrations. cPLA2 is phosphorylated at Ser727 and by a MAPK at Ser505. When phosphorylation is coupled with an influx of calcium ions, PLA2 becomes stimulated and translocates to the membrane where it releases arachidonic acid (AA) from membrane phospholipids. Calcium does not itself activate cPLA2. cPLA2 contains an N-terminal calcium-dependent phospholipid binding domain (CaLB) which shares homology with C2 domains (plays roles in signal transduction and membrane trafficking) and binds it to the membrane. Arachidonic acid is both a signalling molecule and the precursor for other signalling molecules termed eicosanoids (e.g., prostaglandins, leukotrienes and platelet-activating factor). A strict regulation of the activity of phospholipase enzyme is essential.
R-HSA-111883 (Reactome) Once bound to the membrane, cPLA2 hydrolyzes phosphatidylcholine to produce arachidonic acid (AA), a precursor to inflammatory mediators. While several phospholipases can catalyze this reaction in cells overexpressing the enzymes, PLA2G4A is the major enzyme that catalyzes this reaction in vivo (Reed et al. 2011). At the same time, possible physiological roles have been described for soluble phospholipases (sPLA) in the mobilization of arachidonic acid in some cell types or under some physiological conditions (Murakami et al. 2011). Here, the major role of PLA2G4A has been annotated.
R-HSA-111898 (Reactome) ERK2 phosphorylates cPLA2, increasing enzymatic activity. The site of cPLA2 phosphorylation by ERK2 is Ser-505, the major site of cPLA2 phosphorylation observed in phorbol ester-treated cells.
R-HSA-111912 (Reactome) The cAMP-responsive element binding protein (CREB), a key regulator of gene expression, is activated by phosphorylation on Ser-133. Several different protein kinases possess the capability of driving this phosphorylation, making it a point of potential convergence for multiple intracellular signaling cascades. Work in neurons has indicated that physiologic synaptic stimulation recruits a fast calmodulin kinase IV (CaMKIV)-dependent pathway that dominates early signaling to CREB.
R-HSA-111913 (Reactome) CaMKIV becomes fully activated after a three-step mechanism: Upon a transient increase in intracellular calcium, calcium-bound calmodulin (Ca2+/CaM) binds to its autoregulatory domain, which relieves intersteric inhibition. An activating protein kinase, calcium/calmodulin-dependent protein kinase kinase (CaMKK), binds to the Ca2+/CaM:CaMKIV complex and phosphorylates CaMKIV on a threonine residue in the activation loop. After full activation by the three-step mechanism mentioned above, the activity of CaMKIV becomes autonomous and no longer requires bound Ca2+/CaM. This activity is required for CaMKIV-mediated transcriptional regulation. The CaMKIV-associated PP2A then dephosphorylates CaMKIV, thereby terminating autonomous activity and CaMKIV-mediated gene transcription.
R-HSA-111915 (Reactome) Autophosphorylation of the N-terminus Ser12-Ser13 is required for full activation after Ca2+/calmodulin binding and phosphorylation of the Ca2+/calmodulin-bound enzyme on Thr200 by a Ca2+/calmodulin-dependent protein kinase kinase.
R-HSA-111916 (Reactome) CREB readily dimerizes.
R-HSA-111919 (Reactome) cAMP-dependent protein kinase A (PKA) phosphorylates in vitro CREB at a specific residue, serine 133; Phosphorylation of Ser133 is required for signal-induced transcription in vivo.
R-HSA-111924 (Reactome) When cAMP level rises, the PKA catalytic subunit (C subunit) released from the holoenzyme enters the nucleus by passive diffusion whereas termination of signaling to the nucleus involves an active mechanism. In the nucleus, the C subunit binds to the heat-stable protein kinase inhibitor (PKI), and this binding not only inactivates the C subunit but also by conformational change unveils a nuclear export signal in PKI which leads to export of the C-PKI complex from the nucleus.
R-HSA-111925 (Reactome) The four protein kinase A (PKA) regulatory subunit isoforms differ in their tissue specificity and functional characteristics. The specific isoform activated in response to glucagon signalling is not known. The PKA kinase is a tetramer of two regulatory and two catalytic. The regulatory subunits block the catalytic subunits. Binding of cAMP to the regulatory subunit leads to the dissociation of the tetramer into two active dimers made up of a regulatory and a catalytic subunit.
R-HSA-111930 (Reactome) Adenylate cyclase is responsive to calcium and calmodulin and produces cAMP. One important physiological role for Calmodulin is the regulation of adenylylcyclases. Four of the ten known adenylylcyclases are calcium sensitive, in particular type 8 (AC8).
R-HSA-111955 (Reactome) Phosphodiesterases (PDEs) hydrolyze cAMP and cGMP, inactivating these second messengers.
R-HSA-111956 (Reactome) Increased Ca2+ levels, acting via calmodulin, can activate PDE which can then act upon cAMP.
R-HSA-111962 (Reactome) PDE4 hydrolyzes cAMP to AMP.
R-HSA-111966 (Reactome) ADRBK1 (also known as GRK2) is a Serine/Threonine kinase. G-protein-coupled receptor kinases (GRKs) are important regulators of G-protein-coupled receptor function. Binding of calmodulin to ADRBK1 results in inhibition of the kinase activity. This inhibition is almost completely abolished when ADRBK1 is phosphorylated by PKC.
R-HSA-111970 (Reactome) ADRBK1 (also known as GRK2) is phosphorylated at serine 29 in vitro and in vivo by the alpha, gamma and delta isoforms of PKC. PKC-mediated phosphorylation at Ser29 increases ADRBK1 kinase activity towards GPCR substrates, contributing to GPCR desensitization. Phosphorylation at Ser29, which falls within the calmodulin-binding region of ADRBK1, abolishes the inhibitory effect of calmodulin on ADRBK1 kinase activity.
R-HSA-112037 (Reactome) PLC-beta1 is a GTPase-activating protein (GAP) for Gq-alpha, exchanging GTP for GDP and releasing the alpha subunit to cycle back to the membrane and reassociate with the beta-gamma subunits. Between itself and the receptor, they regulate the amplitude of the PLC signal and the rates of signal initiation and termination.
R-HSA-112042 (Reactome) The binding of an opiate peptide to the mu opiate receptor stabilises the receptor conformation in a state of high affinity, both for the ligand itself, and for the G-protein.
R-HSA-112271 (Reactome) The ternary complex neurotransmitter:receptor:G-protein dissociates. Both the alpha-i subunit and beta:gamma complex become active, by conformational transition and surface exposure, and both are free to activate downstream effectors.
R-HSA-112282 (Reactome) The calmodulin:CaMK IV complex enters the nucleus.
R-HSA-167408 (Reactome) The high affinity complex beta-endorphin:mu opioid receptor binds to the heterotrimeric G-protein. This binding stabilises a conformation of the G-protein alpha i subunit presenting a low affinity for GDP, but a high affinity for GTP
R-HSA-167415 (Reactome) Slow intrisinc GTPase activity results in an inactivation of the alpha-i subunit by hydrolyzing GTP to GDP.
R-HSA-167419 (Reactome) G proteins are inactive in the GDP-bound state. The ternary complex neurotransmitter:receptor:G-protein releases GDP.
R-HSA-167427 (Reactome) Different ligands of the MOR receptor can promote MOR phosphorylation, uncoupling, endocytosis or inactivation. For example, the endogenous peptide ligands at the MOR induce rapid desensitization, endocytosis and rapid receptor recycling. By contrast, morphine induces little to no endocytosis, tolerance and dependence. The agonist-dependent phosphorylation of opioid receptors changes the receptor conformation and increases the affinity of the receptors for cytosolic beta-arrestin proteins. This results in an uncoupling of G protein signalling and recruitment of the endocytotic machinery leading to receptor internalization and rapid resensitization. By contrast, PKC phosphorylation by non internalizing opioid ligands (e.g., morphine) cause receptors to remain inactivated in the plasma membrane, leading to signaling desensitization and opioid tolerance. In this case receptors appear to require activity of a phosphatase to be resensitized.
R-HSA-167429 (Reactome) The ternary complex neurotransmitter:receptor:G-protein binds GTP, resulting in activation of G protein.
R-HSA-167433 (Reactome) Gbetagamma rebinds Galpha-olfactory:GDP, stopping its activity
R-HSA-169680 (Reactome) The IP3 receptor (IP3R) is an IP3-gated calcium channel. It is a large, homotetrameric protein, similar to other calcium channel proteins such as ryanodine. The four subunits form a 'four-leafed clover' structure arranged around the central calcium channel. Binding of ligands such as IP3 results in conformational changes in the receptor's structure that leads to channel opening.
R-HSA-169683 (Reactome) IP3 promotes the release of intracellular calcium.
R-HSA-170666 (Reactome) G proteins can deactivate themselves via their intrinsic GTPase activity, which hydrolyzes GTP to GDP. Effectors such as adenylate cyclase can increase the G protein GTPase rate, acting like GTPase-activating proteins (GAPs).
R-HSA-170671 (Reactome) The chronic activation of mu-opioid receptors, which, when coupled to pertussis toxin-sensitive Galpha-i/o proteins, inhibit adenylyl cyclase (AC).
R-HSA-170672 (Reactome) G alpha-olf:GTP binds to inactive adenylate cyclase, causing a conformational transition in adenylate cyclase exposing the catalytic site and activating it.
R-HSA-170674 (Reactome) Once the intrinsic GTPase hydrolyzes GTP to GDP, Galpha-i dissociates from adenylate cyclase, allowing it to re-associate with G-beta-gamma and starting a new cycle.
R-HSA-170676 (Reactome) Once activated, adenylate cyclase utilizes one molecule of ATP to synthesize one molecule of cyclic AMP and pyrophosphate.
R-HSA-170677 (Reactome) Once the intrinsic GTPase hydrolyzes GTP to GDP, Galpha-olf dissociates from adenylate cyclase, allowing it to re-associate with G-beta-gamma and starting a new cycle.
R-HSA-170685 (Reactome) G proteins can deactivate themselves via their intrinsic GTPase activity, which hydrolyzes GTP to GDP. Effectors such as adenylate cyclase can increase the G protein GTPase rate, acting like GTPase-activating proteins (GAPs).
R-HSA-170686 (Reactome) G proteins can deactivate themselves via their intrinsic GTPase activity, which hydrolyzes GTP to GDP. Effectors such as adenylate cyclase can increase the G protein GTPase rate, acting like GTPase-activating proteins (GAPs).
R-HSA-177275 (Reactome) DARPP-32 is phosphorylated by cAMP-dependent protein kinase (PKA) on a single threonine residue, Thr34, resulting in its conversion into a potent inhibitor of protein phosphatase-1.
R-HSA-177284 (Reactome) The phosphorylation of the phosphodiesterase increases its activity, forming a negative feedback loop of the cAMP signal.
R-HSA-180038 (Reactome) DARPP-32 is phosphorylated by cAMP-dependent protein kinase (PKA) on a single threonine residue, Thr34, resulting in its conversion into a potent inhibitor of protein phosphatase-1.
R-HSA-180047 (Reactome) The amino-acid sequence of DARPP-32 contains consensus phosphorylation sites for proline-directed kinases, including Cdk5, a cyclin-dependent kinase family member which is present in post-mitotic neurons expressing high levels of DARPP-32.
R-HSA-180073 (Reactome) DARPP-32 is converted into an inhibitor of protein kinase A (PKA) when phosphorylated at threonine 75 by cyclin-dependent kinase 5 (Cdk5) in brain cells.
R-HSA-201783 (Reactome) PP2B (calcineurin) is a calcium-dependent, calmodulin-stimulated protein phosphatase. It comprises of two components; a catalytic subunit and a regulatory subunit which confers calcium sensitivity to the complex. PP2B is in equilibrium between active and inactive forms. Because the affinity of calmodulin for the active form is higher than for the inactive form, it stabilises PP2B.
R-HSA-201787 (Reactome) Calcineurin has been identified as a Ca2+- and calmodulin-dependent phosphoprotein phosphatase. The concentration of the enzyme is relatively high in mammalian brain.
R-HSA-201790 (Reactome) PP2A is ubiquitously expressed in eukaryotic cells, existing as a heterotrimeric enzyme composed of a 36-kDa catalytic C subunit, a 64-kDa scaffolding A subunit, and multiple regulatory B subunits. The B subunits are thought to influence enzyme activity, substrate specificity, and subcellular localization. PKA phosphorylates PP2A thereby activating the enzyme and is responsible for dopamine/cAMP-dependent dephosphorylation of Thr-75 of DARPP-32.
R-HSA-392206 (Reactome) G-proteins in the Gi class inhibit adenylate cyclase activity, decreasing the production of cAMP from ATP, which has many consequences but classically results in decreased activity of Protein Kinase A (PKA). cAMP also activates the cyclic nucleotide-gated ion channels, a process that is particularly important in olfactory cells.
R-HSA-74448 (Reactome) Upon increase in calcium concentration, calmodulin (CaM) is activated by binding to four calcium ions.
R-HSA-8951727 (Reactome) Protein kinase A (PKA) regulatory subunit isoforms differ in their tissue specificity and functional characteristics. The isoform activated in response to glucagon signalling is not known.

PKA kinase is a tetramer of two regulatory and two catalytic subunits. The regulatory subunits block the activity of the catalytic subunits.

cAMP binds the regulatory subunits, which leads to dissociation of the tetramer into two active dimers made up of a regulatory and a catalytic subunit.
activated PDE1 dimersArrowR-HSA-111956 (Reactome)
activated PDE1 dimersmim-catalysisR-HSA-111955 (Reactome)
active PKC (alpha, gamma, delta)TBarR-HSA-111966 (Reactome)
active PKC (alpha, gamma, delta)mim-catalysisR-HSA-111970 (Reactome)
adenosine 5'-monophosphateArrowR-HSA-111955 (Reactome)
adenosine 5'-monophosphateArrowR-HSA-111962 (Reactome)
cAMP:PKA regulatory subunitArrowR-HSA-111925 (Reactome)
cAMPArrowR-HSA-111930 (Reactome)
cAMPArrowR-HSA-170676 (Reactome)
cAMPR-HSA-111955 (Reactome)
cAMPR-HSA-111962 (Reactome)
cAMPR-HSA-8951727 (Reactome)
p-S133-CREB1ArrowR-HSA-111912 (Reactome)
p-S133-CREB1ArrowR-HSA-111919 (Reactome)
p-S133-CREB1R-HSA-111916 (Reactome)
p-S29-ADRBK1ArrowR-HSA-111970 (Reactome)
p-S505,S727-PLA2G4AArrowR-HSA-111898 (Reactome)
p-S505,S727-PLA2G4AR-HSA-111881 (Reactome)
p-S54-PDE4BArrowR-HSA-177284 (Reactome)
p-T185,Y187-MAPK1mim-catalysisR-HSA-111898 (Reactome)
p-T75-DARPP32s:PRKACAArrowR-HSA-180073 (Reactome)
p-T75-DARPP32sArrowR-HSA-180047 (Reactome)
p-T75-DARPP32sR-HSA-180073 (Reactome)
p-T75-DARPP32sR-HSA-201790 (Reactome)
p-T75-DARPP32sTBarR-HSA-177284 (Reactome)
p-T75-DARPP32smim-catalysisR-HSA-180073 (Reactome)
phospho-CREB dimerArrowR-HSA-111916 (Reactome)
phospho-CaMK IV:CalmodulinArrowR-HSA-111915 (Reactome)
phospho-CaMK IV:Calmodulinmim-catalysisR-HSA-111912 (Reactome)
Personal tools