Opioid signaling (Homo sapiens)

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23, 31, 482, 431, 3403844, 534016, 26, 41, 5029408, 42, 463645, 47243725411, 4052306, 34, 3820402212, 27, 513332, 4910, 199, 2115135403618, 351773314, 28GRK2:calmodulin[plasma membrane](Gialpha1:GTP:Adenylatecyclase):(Galpha-olf:GDP)[plasma membrane]IP3 receptor:IP3complex [endoplasmicreticulum membrane]PP2B catalyticsubunit [cytosol]PP1A(Fe and Mncofactors) [cytosol]G protein alpha:GTPcomplex [plasmamembrane]G protein alpha:GTPcomplex [plasmamembrane]DARPP-32phosporylated on T34[cytosol]G alpha-olf:GTP[plasma membrane]PP2B catalytic(Fe3+, Zn2+):ActiveCalmodulin [cytosol]p-T75-DARPP32s[cytosol]G-protein alpha(i):GDP [plasmamembrane]PP2B catalyticsubunit [cytosol]Protein kinase C(alpha, gamma,delta) [cytosol]Opioid:MOR:Gprotein-GDP complex[plasma membrane]Opioid peptide[extracellularregion]G alpha-olf:GDPcomplex [plasmamembrane]G alpha-olf:GDPcomplex [plasmamembrane]Opioid:MOR [plasmamembrane]G-protein alpha (i)[plasma membrane]Adenylate cyclase(Mg2+ cofactor)[plasma membrane]G-protein beta-gammacomplex [plasmamembrane]PLC-beta [cytosol]Adenylate cyclase(Mg2+ cofactor)[plasma membrane]G protein-GDPcomplex [plasmamembrane]Adenylate cyclase[plasma membrane]PKA regulatorysubunit [cytosol]phospho-CREB dimer[nucleoplasm]G-protein alpha (i):GTP [plasmamembrane]Adenylate cyclase(Mg2+ cofactor)[plasma membrane]Galpha-olf:GTP:Adenylatecyclase (active)complex [plasmamembrane]HeterotrimericG-protein [plasmamembrane]Adenylate cyclase[plasma membrane]G protein alpha:GDPcomplex [plasmamembrane]Phosphorylated (T34)DARPP-32:PP1A[cytosol]G-protein alpha (i)[plasma membrane]G-protein alpha(i/o/z/t) subunit[plasma membrane]Cam-PDE 1 homodimer[cytosol]Opioid:MOR [plasmamembrane]Calmodulin:CaMK IV[nucleoplasm]Adenylate cyclase(Mg2+ cofactor)[plasma membrane]PP2B catalyticsubunit [cytosol]nucleoplasmG protein-GTP[plasma membrane]G-protein alpha (i)[plasma membrane]Active Calmodulin[cytosol]G-protein alpha (i)[plasma membrane]Active Calmodulin[nucleoplasm]G-protein alpha(i):GDP [plasmamembrane]Adenylate cyclase[plasma membrane]IP3 receptors[endoplasmicreticulum membrane]Adenylate cyclase(Mg2+ cofactor)[plasma membrane]PP2B catalytic(Fe3+, Zn2+)[cytosol]Calmodulin:CaMK IV[cytosol]Adenylate cyclase[plasma membrane]p-T75-DARPP32s:PRKACA[cytosol]Adenylate cyclase(Mg2+ cofactor)[plasma membrane]G-protein alpha (i)[plasma membrane]active Cam-PDE 1[cytosol]PP2A-ABdeltaCcomplex [cytosol]Adenylate cyclase[plasma membrane]PP2B catalytic(Fe3+, Zn2+):ActiveCalmodulin [cytosol]Adenylate cyclase[plasma membrane]phospho-CaMKIV:Calmodulin[nucleoplasm]Adenylate cyclase[plasma membrane]G-protein alpha (i):GTP [plasmamembrane]Cam-PDE 1C homodimer[cytosol]PP2B complex[cytosol]Opioid peptide[extracellularregion]G-protein alpha (i):GTP [plasmamembrane]Cam-PDE 1B homodimer[cytosol]cytosolOpioid:MOR:G-proteincomplex [plasmamembrane]Active Calmodulin[cytosol]Opioid:MOR [plasmamembrane]G-protein alpha (i):GTP [plasmamembrane]G-protein alpha(i/o/z/t) subunit[plasma membrane]G-protein alpha(i/o/z/t) subunit[plasma membrane]active PKC (alpha,gamma, delta)[cytosol]Cam-PDE 1A homodimer[cytosol]IP3 receptorhomotetramer[endoplasmicreticulum membrane]G alpha-olf:GDPcomplex [plasmamembrane]Adenylate cyclase[plasma membrane]Opioid:MOR [plasmamembrane]G protein alpha:GDPcomplex [plasmamembrane]Cam-PDE 1 homodimer[cytosol]G-protein alpha(i):GTP:Adenylatecyclase [plasmamembrane]Adenylate cyclase[plasma membrane]G-protein alpha(i):GTP:Adenylatecyclase [plasmamembrane]Adenylate cyclase(Mg2+ cofactor)[plasma membrane]Active Calmodulin[cytosol](Gialpha1:GDP:Adenylatecyclase):(Galpha-olf:GDP)[plasma membrane]Adenylate cyclase(Mg2+ cofactor)[plasma membrane]G-protein alpha:GDP[plasma membrane]cAMP:PKA regulatorysubunit [cytosol]active Calmodulin[nucleoplasm]G-protein beta-gammacomplex [plasmamembrane]PKA tetramer[cytosol]Opioid peptide[extracellularregion]G-protein alpha(i):GTP:Adenylatecyclase [plasmamembrane]Active Calmodulin[cytosol]Opioid peptide[extracellularregion]Cam-PDE 1C homodimer[cytosol]Adenylate cyclase[plasma membrane]IP3 receptorhomotetramer[endoplasmicreticulum membrane]Adenylate cyclase(Mg2+ cofactor)[plasma membrane]G protein alpha:GTPcomplex [plasmamembrane](Gialpha1:GTP:Adenylatecyclase):(Galpha-olf:GTP)[plasma membrane]Activated PLC beta1/4 [plasmamembrane]G-protein beta-gammacomplex [plasmamembrane]G-protein alpha(i/o/z/t) subunit[plasma membrane]Opioid:MOR:Gprotein-GTP complex[plasma membrane]endoplasmic reticulum lumenCam-PDE 1B homodimer[cytosol]ActivePLA2:phosphatidylcholine[endoplasmicreticulum membrane]G alpha-olf:GDPcomplex [plasmamembrane]G-protein alpha (i)[plasma membrane]Galpha-olf:GDP:Adenylatecyclase (active)complex [plasmamembrane]Adenylate cyclase(Mg2+ cofactor)[plasma membrane]Cam-PDE 1A homodimer[cytosol]G-protein alpha(i/o/z/t) subunit[plasma membrane]G alpha-olf:GDPcomplex [plasmamembrane]PKA catalyticsubunit [cytosol]G-protein alpha(i/o/z/t) subunit[plasma membrane]G alpha-olf:GTP[plasma membrane]G-protein beta-gammacomplex [plasmamembrane]IP3 receptors[endoplasmicreticulum membrane]G alpha-olf:GTP[plasma membrane]G protein-GDPcomplex [plasmamembrane]G-protein alpha(i/o/z/t) subunit[plasma membrane]PKA regulatorysubunit [cytosol]PPP3CA [cytosol]Galpha-olf:GDP:Adenylatecyclase (active)complexp-T34,T75,S102,S137-PPP1R1B[cytosol]ADCY9 [plasmamembrane]OPRM1 [plasmamembrane]3',5'-Cyclic AMPAMPOpioid:MOR:Gprotein-GDP complexPRKAR1A(1-381)[cytosol]G alpha-olf:GTPPiADCY5 [plasmamembrane]GNAZ [plasmamembrane]PRKACG [cytosol]GNAI2(2-355) [plasmamembrane]Cam-PDE 1 homodimerADCY6 [plasmamembrane]ADCY7 [plasmamembrane]PPP3R1 [cytosol]PRKACA [cytosol]PRKAR2A [cytosol]ADCY3 [plasmamembrane]PRKAR1B [cytosol]p-T34,S102,S137-PPP1R1B[cytosol](Gialpha1:GTP:Adenylatecyclase):(Galpha-olf:GTP)ADCY2 [plasmamembrane]PRKCG [cytosol]H2OGDP [cytosol]p-T34,T75,S137-PPP1R1B[cytosol]GNAO1 [plasmamembrane]GNAL(2-381) [plasmamembrane]GTP [plasmamembrane]ADCY2 [plasmamembrane]ADCY1 [plasmamembrane]ADCY2 [plasmamembrane]GNAL(2-381) [plasmamembrane]OPRM1 [plasmamembrane]GNAL(2-381) [plasmamembrane]ADCY7 [plasmamembrane]ADCY2 [plasmamembrane]CAMK4 [nucleoplasm]PDE1C [cytosol]I(1,4,5)P3ADCY5 [plasmamembrane]DARPP-32 (for CDK5phosphorylation)Arachidonic acidGNAO1 [plasmamembrane]ADCY8 [plasmamembrane]PPP2R5D [cytosol]PRKAR2B [cytosol]p-T34,S102-PPP1R1B[cytosol]ADCY9 [plasmamembrane]Ca2+ [cytosol]CALM1 [cytosol]ADCY5 [plasmamembrane]ADCY8 [plasmamembrane]ADCY3 [plasmamembrane]G protein-GDPcomplexATPGNAT3(2-354) [plasmamembrane]ITPR2 [endoplasmicreticulum membrane]ADCY1 [plasmamembrane]PPiGNAT3(2-354) [plasmamembrane]H2OCALM1 [cytosol]Opioid peptidep-S133-CREB1[nucleoplasm]ADCY4 [plasmamembrane]ADCY3 [plasmamembrane]p-S505,S727-PLA2G4AGNAT1 [plasmamembrane]Mg2+ [plasmamembrane]GDP [cytosol]ADCY6 [plasmamembrane]GNAI1(2-354) [plasmamembrane](Gialpha1:GTP:Adenylatecyclase):(Galpha-olf:GDP)GNAT3(2-354) [plasmamembrane]ADCY7 [plasmamembrane]p-T75-PPP1R1B[cytosol]GNAO1 [plasmamembrane]ADCY9 [plasmamembrane]p-S12,S13-CAMK4[nucleoplasm]Calmodulin:CaMK IVG-protein alpha (i):GTPMg2+ [plasmamembrane]PDYN(226-230)[extracellularregion]PRKCA [cytosol]H2OCREB1GNAI3(2-354) [plasmamembrane]Phosphorylated (T34)DARPP-32:PP1APDE1A [cytosol]ADCY2 [plasmamembrane]GTP [plasmamembrane]PLCB1 [cytosol]3',5'-Cyclic AMPGNAI3(2-354) [plasmamembrane]GNAL(2-381) [plasmamembrane]PLCB3(2-1234)[cytosol]GNAI3(2-354) [plasmamembrane]ADCY4 [plasmamembrane]ADCY2 [plasmamembrane]Opioid:MOR:G-proteincomplexADCY1 [plasmamembrane]p-T34,T75,S137-PPP1R1B[cytosol]CALM1 [nucleoplasm]ADCY8 [plasmamembrane]ADCY8 [plasmamembrane]GNAI1(2-354) [plasmamembrane]Protein Kinase A,catalytic subunitsPRKACA [cytosol]PiCAMK4 [cytosol]GTP [cytosol]Adenylate cyclase(Mg2+ cofactor)CALM1ADCY1 [plasmamembrane]DAGsCa2+ [nucleoplasm]PP2A-ABdeltaCcomplexPPP3CB(2-524)[cytosol]CALM1 [nucleoplasm]Ca2+ [cytosol]GNAT2(2-354) [plasmamembrane]PPP3CA [cytosol]GNAO1 [plasmamembrane]GNAI1(2-354) [plasmamembrane]GNAI1(2-354) [plasmamembrane]ADCY4 [plasmamembrane]p-S54-PDE4BFe3+ [cytosol]Active CalmodulinGNAI3(2-354) [plasmamembrane]ADCY1 [plasmamembrane]GNAO1 [plasmamembrane]POMC(237-241)[extracellularregion]ADCY7 [plasmamembrane]GNAT1 [plasmamembrane]OPRM1PLC-betaPPP3CA [cytosol]GNAI3(2-354) [plasmamembrane]ADCY8 [plasmamembrane]ADCY8 [plasmamembrane]ADCY9 [plasmamembrane]Zn2+ [cytosol]ADCY3 [plasmamembrane]PKA catalyticsubunitADCY7 [plasmamembrane]Mg2+ [plasmamembrane]cAMP:PKA regulatorysubunitGNAZ [plasmamembrane]p-T34,T75-PPP1R1B[cytosol]PRKCD(1-676)[cytosol](Gialpha1:GDP:Adenylatecyclase):(Galpha-olf:GDP)Mg2+ [plasmamembrane]Opioid:MOR:Gprotein-GTP complexADCY8 [plasmamembrane]Mg2+ [plasmamembrane]ADCY3 [plasmamembrane]GTPGNAI2(2-355) [plasmamembrane]Ca2+ [cytosol]GNAT1 [plasmamembrane]GNAO1 [plasmamembrane]Mg2+ [plasmamembrane]POMC(237-241)[extracellularregion]POMC(237-267)[extracellularregion]CDK5ADCY9 [plasmamembrane]p-T34,S137-PPP1R1B[cytosol]GNAT3(2-354) [plasmamembrane]p-S133-CREB1GNAI3(2-354) [plasmamembrane]PDE1B [cytosol]ActivePLA2:phosphatidylcholineITPR3 [endoplasmicreticulum membrane]GNAI1(2-354) [plasmamembrane]ADCY8 [plasmamembrane]ATPPRKAR2A [cytosol]GNAT2(2-354) [plasmamembrane]G alpha-olf:GDPcomplexH2OG-protein beta-gammacomplexGNAT2(2-354) [plasmamembrane]PDYN(226-230)[extracellularregion]GNAZ [plasmamembrane]ADCY2 [plasmamembrane]ADCY2 [plasmamembrane]ADCY6 [plasmamembrane]Ca2+ [cytosol]ADCY3 [plasmamembrane]H2Op-T34,T75-PPP1R1B[cytosol]GTP [cytosol]ITPR1 [endoplasmicreticulum membrane]IP3 receptorhomotetramerGRK2:calmodulinPPP3CC [cytosol]GDP [plasmamembrane]GNAI3(2-354) [plasmamembrane]ATPG protein alpha:GTPcomplexGNAZ [plasmamembrane]PRKAR1A(1-381)[cytosol]PDYN(226-230)[extracellularregion]ITPR3 [endoplasmicreticulum membrane]2-LysophosphatidylcholineADCY7 [plasmamembrane]POMC(237-267)[extracellularregion]GTPADCY4 [plasmamembrane]GNAZ [plasmamembrane]ATPp-S133-CREB1PDE 4PLCB2 [cytosol]GNAI1(2-354) [plasmamembrane]OPRM1 [plasmamembrane]ADCY6 [plasmamembrane]PRKAR2B [cytosol]POMC(237-267)[extracellularregion]ADPGNAZ [plasmamembrane]GDPGTP [plasmamembrane]IP3 receptor:IP3complexADCY1 [plasmamembrane]OPRM1 [plasmamembrane]H2OADCY2 [plasmamembrane]ADCY9 [plasmamembrane]ADCY4 [plasmamembrane]ADCY5 [plasmamembrane]GTP [cytosol]CALM1 [cytosol]GDP [cytosol]GNAT2(2-354) [plasmamembrane]PPP1CA [cytosol]ADCY1 [plasmamembrane]GNAI3(2-354) [plasmamembrane]p-S29-ADRBK1(2-689)PP2B catalytic(Fe3+, Zn2+):ActiveCalmodulinPKA tetramerGNAT1 [plasmamembrane]GNAT1 [plasmamembrane]Mg2+ [plasmamembrane]GNAI3(2-354) [plasmamembrane]GNAI3(2-354) [plasmamembrane]ADCY3 [plasmamembrane]PiGNAI3(2-354) [plasmamembrane]Fe2+ [cytosol]GNAL(2-381) [plasmamembrane]p-T34-PPP1R1B[cytosol]ADRBK1(2-689)Adenylate cyclase(Mg2+ cofactor)GNAT3(2-354) [plasmamembrane]Activated PLC beta1/4GNAT3(2-354) [plasmamembrane]p-T75,S102-PPP1R1B[cytosol]GTP [cytosol]active PKC (alpha,gamma, delta)GNAI1(2-354) [plasmamembrane]GNAL(2-381) [plasmamembrane]ATPADCY1 [plasmamembrane]GTP [plasmamembrane]ADCY4 [plasmamembrane]phospho-CaMKIV:CalmodulinGNAI1(2-354) [plasmamembrane]ADPG-protein alpha:GDPPPP3CB(2-524)[cytosol]ADCY7 [plasmamembrane]PKA catalyticsubunitADCY1 [plasmamembrane]PiPRKACB [cytosol]ATPADCY3 [plasmamembrane]GNAI2(2-355) [plasmamembrane]phospho-CREB dimerGNAT2(2-354) [plasmamembrane]ADCY9 [plasmamembrane]ADCY5 [plasmamembrane]G-protein alpha(i):GTP:AdenylatecyclaseCa2+ [cytosol]GNAI1(2-354) [plasmamembrane]CAMK4PDYN(226-230)[extracellularregion]GNAI2(2-355) [plasmamembrane]POMC(237-267)[extracellularregion]ATPPDE1B [cytosol]PCPC [endoplasmicreticulum membrane]GTP [cytosol]PP2B complexADCY5 [plasmamembrane]CALM1 [cytosol]ADCY6 [plasmamembrane]ADCY7 [plasmamembrane]PPP3CB(2-524)[cytosol]GDP [cytosol]ADCY4 [plasmamembrane]ADCY9 [plasmamembrane]GNAT3(2-354) [plasmamembrane]GNAI2(2-355) [plasmamembrane]POMC(237-241)[extracellularregion]Zn2+ [cytosol]GNAT3(2-354) [plasmamembrane]ADCY1 [plasmamembrane]GNAI1(2-354) [plasmamembrane]3',5'-Cyclic AMPGNAI2(2-355) [plasmamembrane]GNAI2(2-355) [plasmamembrane]Calmodulin:CaMK IVADCY6 [plasmamembrane]ADCY3 [plasmamembrane]PPP3CC [cytosol]ADPGNAI3(2-354) [plasmamembrane]p-T34,T75,S102-PPP1R1B[cytosol]p-T75,S102,S137-PPP1R1B[cytosol]Galpha-olf:GTP:Adenylatecyclase (active)complexPDE1A [cytosol]ADCY6 [plasmamembrane]GDP [cytosol]p-T185,Y187-MAPK1ADCY6 [plasmamembrane]PLCB4 [cytosol]Mg2+ [plasmamembrane]GNAT3(2-354) [plasmamembrane]GNAI2(2-355) [plasmamembrane]GNAT3(2-354) [plasmamembrane]PDE1C [cytosol]active Cam-PDE 1GDP [cytosol]PhosphatidylcholineGNAI1(2-354) [plasmamembrane]ADPGNAL(2-381) [plasmamembrane]ADCY4 [plasmamembrane]GNAI3(2-354) [plasmamembrane]I(1,4,5)P3 [cytosol]ADCY7 [plasmamembrane]Fe3+ [cytosol]Adenylate cyclase(Mg2+ cofactor)GDP [plasmamembrane]Mn2+ [cytosol]Ca2+ [nucleoplasm]Fe3+ [cytosol]GNAL(2-381) [plasmamembrane]p-T34,T75,S102-PPP1R1B[cytosol]Mg2+ [plasmamembrane]GNAT1 [plasmamembrane]GNAI1(2-354) [plasmamembrane]GNAT1 [plasmamembrane]GNAT2(2-354) [plasmamembrane]ATPp-T75-DARPP32sPRKAR1B [cytosol]ADCY5 [plasmamembrane]DARPP-32 (and/orphosphorylated)p-T34,T75,S102,S137-PPP1R1B[cytosol]GNAT3(2-354) [plasmamembrane]G-protein alpha(i/o/z/t) subunitPPP1CAPRKACAGDPGNAI2(2-355) [plasmamembrane]ADCY9 [plasmamembrane]ADCY9 [plasmamembrane]G alpha-olf:GDPcomplexPOMC(237-241)[extracellularregion]ATPGNAI2(2-355) [plasmamembrane]ADCY5 [plasmamembrane]ADRBK1(2-689)[plasma membrane]ADPGNAT3(2-354) [plasmamembrane]GDP [cytosol]GNAO1 [plasmamembrane]ITPR2 [endoplasmicreticulum membrane]3',5'-Cyclic AMP[cytosol]p-S505,S727-PLA2G4A[endoplasmicreticulum membrane]ITPR1 [endoplasmicreticulum membrane]ADCY8 [plasmamembrane]ADCY7 [plasmamembrane]ADP3',5'-Cyclic AMPGNAI1(2-354) [plasmamembrane]ADPPPiGNAI2(2-355) [plasmamembrane]GNAZ [plasmamembrane]GNAT2(2-354) [plasmamembrane]PLA2G4ACa2+ [cytosol]DARPP-32phosporylated on T34CREB1ADCY6 [plasmamembrane]Ca2+GDP [cytosol]Opioid:MORZn2+ [cytosol]Adenylate cyclase(Mg2+ cofactor)p-T75-DARPP32s:PRKACAG-protein alpha(i):GDPADCY4 [plasmamembrane]PPP3CC [cytosol]ADCY6 [plasmamembrane]CALM1 [cytosol]ADCY8 [plasmamembrane]ADCY2 [plasmamembrane]GNAI2(2-355) [plasmamembrane]H2OADCY3 [plasmamembrane]GTP [cytosol]ADCY5 [plasmamembrane]GNAI2(2-355) [plasmamembrane]p-T75,S137-PPP1R1B[cytosol]Mg2+ [plasmamembrane]PI(4,5)P2AMPPDE4BGNAT3(2-354) [plasmamembrane]PP2B catalytic(Fe3+, Zn2+)ADCY5 [plasmamembrane]Ca2+PiADCY4 [plasmamembrane]39


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). Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=111885

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  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)		ComplexREACT_15896 (Reactome)
(Gi

alpha1:GTP:Adenylate cyclase):(G

alpha-olf:GDP)		ComplexREACT_15853 (Reactome)
(Gi

alpha1:GTP:Adenylate cyclase):(G

alpha-olf:GTP)		ComplexREACT_15996 (Reactome)
2-LysophosphatidylcholineCHEBI:17504 (ChEBI)
3',5'-Cyclic AMP [cytosol]MetaboliteCHEBI:17489 (ChEBI)
3',5'-Cyclic AMPMetaboliteCHEBI:17489 (ChEBI)
ADCY1 [plasma membrane]ProteinQ08828 (Uniprot-TrEMBL)
ADCY2 [plasma membrane]ProteinQ08462 (Uniprot-TrEMBL)
ADCY3 [plasma membrane]ProteinO60266 (Uniprot-TrEMBL)
ADCY4 [plasma membrane]ProteinQ8NFM4 (Uniprot-TrEMBL)
ADCY5 [plasma membrane]ProteinO95622 (Uniprot-TrEMBL)
ADCY6 [plasma membrane]ProteinO43306 (Uniprot-TrEMBL)
ADCY7 [plasma membrane]ProteinP51828 (Uniprot-TrEMBL)
ADCY8 [plasma membrane]ProteinP40145 (Uniprot-TrEMBL)
ADCY9 [plasma membrane]ProteinO60503 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
ADRBK1(2-689) [plasma membrane]ProteinP25098 (Uniprot-TrEMBL)
ADRBK1(2-689)ProteinP25098 (Uniprot-TrEMBL)
AMPMetaboliteCHEBI:16027 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated PLC beta 1/4ComplexREACT_15568 (Reactome)
Active PLA2:phosphatidylcholineComplexREACT_15631 (Reactome)
Active CalmodulinComplexREACT_3178 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ComplexREACT_17689 (Reactome)
Arachidonic acidMetaboliteCHEBI:15843 (ChEBI)
CALM1 [cytosol]ProteinP62158 (Uniprot-TrEMBL)
CALM1 [nucleoplasm]ProteinP62158 (Uniprot-TrEMBL)
CALM1ProteinP62158 (Uniprot-TrEMBL)
CAMK4 [cytosol]ProteinQ16566 (Uniprot-TrEMBL)
CAMK4 [nucleoplasm]ProteinQ16566 (Uniprot-TrEMBL)
CAMK4ProteinQ16566 (Uniprot-TrEMBL)
CDK5ProteinQ00535 (Uniprot-TrEMBL)
CREB1ProteinP16220 (Uniprot-TrEMBL)
Ca2+ [cytosol]MetaboliteCHEBI:29108 (ChEBI)
Ca2+ [nucleoplasm]MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Calmodulin:CaMK IVComplexREACT_15739 (Reactome)
Calmodulin:CaMK IVComplexREACT_15747 (Reactome)
Cam-PDE 1 homodimerComplexREACT_5507 (Reactome)
DAGsMetaboliteCHEBI:18035 (ChEBI)
DARPP-32 phosporylated on T34ProteinREACT_15578 (Reactome)
DARPP-32 (and/or phosphorylated)ProteinREACT_17763 (Reactome)
DARPP-32 (for CDK5 phosphorylation)ProteinREACT_17935 (Reactome)
Fe2+ [cytosol]MetaboliteCHEBI:18248 (ChEBI)
Fe3+ [cytosol]MetaboliteCHEBI:29034 (ChEBI)
G

alpha-olf:GDP:Adenylate cyclase (active)

complex		ComplexREACT_15796 (Reactome)
G

alpha-olf:GTP:Adenylate cyclase (active)

complex		ComplexREACT_17212 (Reactome)
G alpha-olf:GDP complexComplexREACT_17352 (Reactome)
G alpha-olf:GTPComplexREACT_16015 (Reactome)
G protein alpha:GTP complexComplexREACT_17389 (Reactome)
G protein-GDP complexComplexREACT_15793 (Reactome)
G-protein alpha (i):GDPComplexREACT_19806 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase		ComplexREACT_19914 (Reactome)
G-protein alpha (i/o/z/t) subunitProteinREACT_16054 (Reactome)
G-protein alpha (i): GTPComplexREACT_19580 (Reactome)
G-protein alpha:GDPComplexREACT_17952 (Reactome)
G-protein beta-gamma complexComplexREACT_15674 (Reactome)
GDP [cytosol]MetaboliteCHEBI:17552 (ChEBI)
GDP [plasma membrane]MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GNAI1(2-354) [plasma membrane]ProteinP63096 (Uniprot-TrEMBL)
GNAI2(2-355) [plasma membrane]ProteinP04899 (Uniprot-TrEMBL)
GNAI3(2-354) [plasma membrane]ProteinP08754 (Uniprot-TrEMBL)
GNAL(2-381) [plasma membrane]ProteinP38405 (Uniprot-TrEMBL)
GNAO1 [plasma membrane]ProteinP09471 (Uniprot-TrEMBL)
GNAT1 [plasma membrane]ProteinP11488 (Uniprot-TrEMBL)
GNAT2(2-354) [plasma membrane]ProteinP19087 (Uniprot-TrEMBL)
GNAT3(2-354) [plasma membrane]ProteinA8MTJ3 (Uniprot-TrEMBL)
GNAZ [plasma membrane]ProteinP19086 (Uniprot-TrEMBL)
GRK2:calmodulinComplexREACT_17570 (Reactome)
GTP [cytosol]MetaboliteCHEBI:15996 (ChEBI)
GTP [plasma membrane]MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
I(1,4,5)P3 [cytosol]MetaboliteCHEBI:16595 (ChEBI)
I(1,4,5)P3MetaboliteCHEBI:16595 (ChEBI)
IP3 receptor homotetramerComplexREACT_12247 (Reactome)
IP3 receptor:IP3 complexComplexREACT_12249 (Reactome)
ITPR1 [endoplasmic reticulum membrane]ProteinQ14643 (Uniprot-TrEMBL)
ITPR2 [endoplasmic reticulum membrane]ProteinQ14571 (Uniprot-TrEMBL)
ITPR3 [endoplasmic reticulum membrane]ProteinQ14573 (Uniprot-TrEMBL)
Mg2+ [plasma membrane]MetaboliteCHEBI:18420 (ChEBI)
Mn2+ [cytosol]MetaboliteCHEBI:18291 (ChEBI)
OPRM1 [plasma membrane]ProteinP35372 (Uniprot-TrEMBL)
OPRM1ProteinP35372 (Uniprot-TrEMBL)
Opioid peptideProteinREACT_15976 (Reactome)
Opioid:MOR:G protein-GDP complexComplexREACT_15815 (Reactome)
Opioid:MOR:G protein-GTP complexComplexREACT_15831 (Reactome)
Opioid:MOR:G-protein complexComplexREACT_15585 (Reactome)
Opioid:MORComplexREACT_15680 (Reactome)
PC [endoplasmic reticulum membrane]MetaboliteCHEBI:16110 (ChEBI)
PCMetaboliteCHEBI:16110 (ChEBI)
PDE 4REACT_5541 (Reactome) cAMP selective hydrolase
PDE1A [cytosol]ProteinP54750 (Uniprot-TrEMBL) Can hydrolyze both cAMP and cGMP
PDE1B [cytosol]ProteinQ01064 (Uniprot-TrEMBL) Can hydrolyze both cAMP and cGMP
PDE1C [cytosol]ProteinQ14123 (Uniprot-TrEMBL)
PDE4BProteinQ07343 (Uniprot-TrEMBL)
PDYN(226-230)

[extracellular

region]		ProteinP01213 (Uniprot-TrEMBL)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PKA catalytic subunitProteinREACT_3031 (Reactome)
PKA tetramerComplexREACT_5749 (Reactome)
PLA2G4AProteinP47712 (Uniprot-TrEMBL)
PLC-betaProteinREACT_15673 (Reactome)
PLCB1 [cytosol]ProteinQ9NQ66 (Uniprot-TrEMBL)
PLCB2 [cytosol]ProteinQ00722 (Uniprot-TrEMBL)
PLCB3(2-1234) [cytosol]ProteinQ01970 (Uniprot-TrEMBL)
PLCB4 [cytosol]ProteinQ15147 (Uniprot-TrEMBL)
POMC(237-241)

[extracellular

region]		ProteinP01189 (Uniprot-TrEMBL)
POMC(237-267)

[extracellular

region]		ProteinP01189 (Uniprot-TrEMBL)
PP2A-ABdeltaC complexComplexREACT_5648 (Reactome)
PP2B catalytic

(Fe3+, Zn2+):Active

Calmodulin		ComplexREACT_17373 (Reactome)
PP2B catalytic (Fe3+, Zn2+)ComplexREACT_18243 (Reactome)
PP2B complexComplexREACT_17149 (Reactome)
PPP1CA [cytosol]ProteinP62136 (Uniprot-TrEMBL)
PPP1CAProteinP62136 (Uniprot-TrEMBL)
PPP2R5D [cytosol]ProteinQ14738 (Uniprot-TrEMBL)
PPP3CA [cytosol]ProteinQ08209 (Uniprot-TrEMBL)
PPP3CB(2-524) [cytosol]ProteinP16298 (Uniprot-TrEMBL)
PPP3CC [cytosol]ProteinP48454 (Uniprot-TrEMBL)
PPP3R1 [cytosol]ProteinP63098 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKACA [cytosol]ProteinP17612 (Uniprot-TrEMBL)
PRKACAProteinP17612 (Uniprot-TrEMBL)
PRKACB [cytosol]ProteinP22694 (Uniprot-TrEMBL)
PRKACG [cytosol]ProteinP22612 (Uniprot-TrEMBL)
PRKAR1A(1-381) [cytosol]ProteinP10644 (Uniprot-TrEMBL)
PRKAR1B [cytosol]ProteinP31321 (Uniprot-TrEMBL)
PRKAR2A [cytosol]ProteinP13861 (Uniprot-TrEMBL)
PRKAR2B [cytosol]ProteinP31323 (Uniprot-TrEMBL)
PRKCA [cytosol]ProteinP17252 (Uniprot-TrEMBL)
PRKCD(1-676) [cytosol]ProteinQ05655 (Uniprot-TrEMBL)
PRKCG [cytosol]ProteinP05129 (Uniprot-TrEMBL)
PhosphatidylcholineCHEBI:16110 (ChEBI)
Phosphorylated (T34) DARPP-32:PP1AComplexREACT_17348 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)
Protein Kinase A, catalytic subunitsProteinREACT_2480 (Reactome)
Zn2+ [cytosol]MetaboliteCHEBI:29105 (ChEBI)
active Cam-PDE 1ComplexREACT_3728 (Reactome)
active PKC (alpha, gamma, delta)ComplexREACT_16103 (Reactome)
cAMP:PKA regulatory subunitComplexREACT_4571 (Reactome)
p-S12,S13-CAMK4 [nucleoplasm]ProteinQ16566 (Uniprot-TrEMBL)
p-S133-CREB1 [nucleoplasm]ProteinP16220 (Uniprot-TrEMBL)
p-S133-CREB1ProteinP16220 (Uniprot-TrEMBL)
p-S29-ADRBK1(2-689)ProteinP25098 (Uniprot-TrEMBL)
p-S505,S727-PLA2G4A

[endoplasmic

reticulum membrane]		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 [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,S102-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,S137-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75,S102,S137-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75,S102-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75,S137-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34,T75-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T34-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75,S102,S137-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75,S102-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75,S137-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
p-T75-DARPP32s:PRKACAComplexREACT_17157 (Reactome)
p-T75-DARPP32sProteinREACT_16096 (Reactome)
p-T75-PPP1R1B [cytosol]ProteinQ9UD71 (Uniprot-TrEMBL)
phospho-CREB dimerComplexREACT_17630 (Reactome)
phospho-CaMK IV:CalmodulinComplexREACT_15743 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
(Gi

alpha1:GDP:Adenylate cyclase):(G

alpha-olf:GDP)		ArrowREACT_15495 (Reactome)
(Gi

alpha1:GDP:Adenylate cyclase):(G

alpha-olf:GDP)		REACT_15384 (Reactome)
(Gi

alpha1:GTP:Adenylate cyclase):(G

alpha-olf:GDP)		ArrowREACT_15335 (Reactome)
(Gi

alpha1:GTP:Adenylate cyclase):(G

alpha-olf:GTP)		ArrowREACT_15435 (Reactome)
(Gi

alpha1:GTP:Adenylate cyclase):(G

alpha-olf:GTP)		REACT_15335 (Reactome)
(Gi

alpha1:GTP:Adenylate cyclase):(G

alpha-olf:GTP)		REACT_15495 (Reactome)
(Gi

alpha1:GTP:Adenylate cyclase):(G

alpha-olf:GTP)		mim-catalysisREACT_15335 (Reactome)
(Gi

alpha1:GTP:Adenylate cyclase):(G

alpha-olf:GTP)		mim-catalysisREACT_15495 (Reactome)
2-LysophosphatidylcholineArrowREACT_15331 (Reactome)
3',5'-Cyclic AMPArrowREACT_15399 (Reactome)
3',5'-Cyclic AMPArrowREACT_1963 (Reactome)
3',5'-Cyclic AMPREACT_1257 (Reactome)
3',5'-Cyclic AMPREACT_1532 (Reactome)
3',5'-Cyclic AMPREACT_827 (Reactome)
ADPArrowREACT_15320 (Reactome)
ADPArrowREACT_15377 (Reactome)
ADPArrowREACT_15427 (Reactome)
ADPArrowREACT_15519 (Reactome)
ADPArrowREACT_15529 (Reactome)
ADPArrowREACT_15534 (Reactome)
ADPArrowREACT_23990 (Reactome)
ADRBK1(2-689)REACT_15422 (Reactome)
ADRBK1(2-689)REACT_15534 (Reactome)
AMPArrowREACT_1257 (Reactome)
AMPArrowREACT_827 (Reactome)
ATPREACT_15320 (Reactome)
ATPREACT_15377 (Reactome)
ATPREACT_15399 (Reactome)
ATPREACT_15427 (Reactome)
ATPREACT_15519 (Reactome)
ATPREACT_15529 (Reactome)
ATPREACT_15534 (Reactome)
ATPREACT_1963 (Reactome)
ATPREACT_23990 (Reactome)
Activated PLC beta 1/4ArrowREACT_15402 (Reactome)
Activated PLC beta 1/4REACT_15301 (Reactome)
Activated PLC beta 1/4mim-catalysisREACT_15353 (Reactome)
Active PLA2:phosphatidylcholineArrowREACT_15311 (Reactome)
Active PLA2:phosphatidylcholinemim-catalysisREACT_15331 (Reactome)
Active CalmodulinArrowREACT_12602 (Reactome)
Active CalmodulinArrowREACT_15450 (Reactome)
Active CalmodulinREACT_15299 (Reactome)
Active CalmodulinREACT_15339 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ArrowREACT_15384 (Reactome)
Adenylate cyclase (Mg2+ cofactor)ArrowREACT_15547 (Reactome)
Adenylate cyclase (Mg2+ cofactor)REACT_15385 (Reactome)
Adenylate cyclase (Mg2+ cofactor)REACT_19222 (Reactome)
Adenylate cyclase (Mg2+ cofactor)mim-catalysisREACT_15385 (Reactome)
Adenylate cyclase (Mg2+ cofactor)mim-catalysisREACT_1963 (Reactome)
Arachidonic acidArrowREACT_15331 (Reactome)
CALM1REACT_12602 (Reactome)
CALM1REACT_15422 (Reactome)
CAMK4REACT_15339 (Reactome)
CDK5mim-catalysisREACT_15365 (Reactome)
CREB1REACT_15377 (Reactome)
CREB1REACT_15427 (Reactome)
Ca2+ArrowREACT_12074 (Reactome)
Ca2+REACT_12074 (Reactome)
Ca2+REACT_12602 (Reactome)
Ca2+REACT_15311 (Reactome)
Calmodulin:CaMK IVArrowREACT_15332 (Reactome)
Calmodulin:CaMK IVArrowREACT_15339 (Reactome)
Calmodulin:CaMK IVREACT_15320 (Reactome)
Calmodulin:CaMK IVREACT_15332 (Reactome)
Calmodulin:CaMK IVmim-catalysisREACT_15320 (Reactome)
Cam-PDE 1 homodimerREACT_15450 (Reactome)
DAGsArrowREACT_15353 (Reactome)
DARPP-32 phosporylated on T34ArrowREACT_15529 (Reactome)
DARPP-32 phosporylated on T34REACT_15494 (Reactome)
DARPP-32 phosporylated on T34REACT_15496 (Reactome)
DARPP-32 (and/or phosphorylated)ArrowREACT_15494 (Reactome)
DARPP-32 (and/or phosphorylated)REACT_15529 (Reactome)
DARPP-32 (for CDK5 phosphorylation)ArrowREACT_15438 (Reactome)
DARPP-32 (for CDK5 phosphorylation)REACT_15365 (Reactome)
G

alpha-olf:GDP:Adenylate cyclase (active)

complex		ArrowREACT_15449 (Reactome)
G

alpha-olf:GDP:Adenylate cyclase (active)

complex		REACT_15547 (Reactome)
G

alpha-olf:GTP:Adenylate cyclase (active)

complex		ArrowREACT_15385 (Reactome)
G

alpha-olf:GTP:Adenylate cyclase (active)

complex		REACT_15449 (Reactome)
G

alpha-olf:GTP:Adenylate cyclase (active)

complex		mim-catalysisREACT_15399 (Reactome)
G

alpha-olf:GTP:Adenylate cyclase (active)

complex		mim-catalysisREACT_15449 (Reactome)
G alpha-olf:GDP complexArrowREACT_15384 (Reactome)
G alpha-olf:GDP complexArrowREACT_15547 (Reactome)
G alpha-olf:GTPREACT_15385 (Reactome)
G alpha-olf:GTPREACT_15435 (Reactome)
G protein alpha:GTP complexArrowREACT_15336 (Reactome)
G protein alpha:GTP complexREACT_15316 (Reactome)
G protein alpha:GTP complexREACT_15402 (Reactome)
G protein-GDP complexArrowREACT_15387 (Reactome)
G protein-GDP complexREACT_15298 (Reactome)
G-protein alpha (i):GDPArrowREACT_15384 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase		ArrowREACT_19222 (Reactome)
G-protein alpha

(i):GTP:Adenylate

cyclase		REACT_15435 (Reactome)
G-protein alpha (i/o/z/t) subunitmim-catalysisREACT_15316 (Reactome)
G-protein alpha (i/o/z/t) subunitmim-catalysisREACT_15491 (Reactome)
G-protein alpha (i): GTPREACT_19222 (Reactome)
G-protein alpha:GDPArrowREACT_15301 (Reactome)
G-protein alpha:GDPArrowREACT_15316 (Reactome)
G-protein alpha:GDPREACT_15387 (Reactome)
G-protein beta-gamma complexArrowREACT_15336 (Reactome)
G-protein beta-gamma complexREACT_15387 (Reactome)
GDPArrowREACT_15549 (Reactome)
GDPREACT_15316 (Reactome)
GRK2:calmodulinArrowREACT_15422 (Reactome)
GTPArrowREACT_15316 (Reactome)
GTPREACT_15491 (Reactome)
H2OREACT_1257 (Reactome)
H2OREACT_15301 (Reactome)
H2OREACT_15331 (Reactome)
H2OREACT_15353 (Reactome)
H2OREACT_15438 (Reactome)
H2OREACT_15494 (Reactome)
H2OREACT_827 (Reactome)
I(1,4,5)P3ArrowREACT_12074 (Reactome)
I(1,4,5)P3ArrowREACT_15353 (Reactome)
I(1,4,5)P3REACT_12008 (Reactome)
IP3 receptor homotetramerREACT_12008 (Reactome)
IP3 receptor:IP3 complexArrowREACT_12008 (Reactome)
IP3 receptor:IP3 complexmim-catalysisREACT_12074 (Reactome)
OPRM1ArrowREACT_15388 (Reactome)
OPRM1REACT_15473 (Reactome)
Opioid peptideArrowREACT_15388 (Reactome)
Opioid peptideREACT_15473 (Reactome)
Opioid:MOR:G protein-GDP complexArrowREACT_15298 (Reactome)
Opioid:MOR:G protein-GDP complexREACT_15549 (Reactome)
Opioid:MOR:G protein-GTP complexArrowREACT_15491 (Reactome)
Opioid:MOR:G protein-GTP complexREACT_15336 (Reactome)
Opioid:MOR:G-protein complexArrowREACT_15549 (Reactome)
Opioid:MOR:G-protein complexREACT_15491 (Reactome)
Opioid:MORArrowREACT_15336 (Reactome)
Opioid:MORArrowREACT_15473 (Reactome)
Opioid:MORREACT_15298 (Reactome)
Opioid:MORREACT_15388 (Reactome)
Opioid:MORmim-catalysisREACT_15298 (Reactome)
PCREACT_15311 (Reactome)
PDE 4mim-catalysisREACT_1257 (Reactome)
PDE4BREACT_15519 (Reactome)
PI(4,5)P2REACT_15353 (Reactome)
PKA catalytic subunitArrowREACT_1532 (Reactome)
PKA catalytic subunitREACT_1031 (Reactome)
PKA tetramerREACT_1532 (Reactome)
PLA2G4AREACT_23990 (Reactome)
PLC-betaArrowREACT_15301 (Reactome)
PLC-betaREACT_15402 (Reactome)
PP2A-ABdeltaC complexmim-catalysisREACT_15438 (Reactome)
PP2B catalytic

(Fe3+, Zn2+):Active

Calmodulin		ArrowREACT_15299 (Reactome)
PP2B catalytic (Fe3+, Zn2+)REACT_15299 (Reactome)
PP2B complexmim-catalysisREACT_15494 (Reactome)
PPP1CAREACT_15496 (Reactome)
PPiArrowREACT_15399 (Reactome)
PPiArrowREACT_1963 (Reactome)
PRKACAREACT_15540 (Reactome)
PRKACAmim-catalysisREACT_15519 (Reactome)
PRKACAmim-catalysisREACT_15529 (Reactome)
PhosphatidylcholineREACT_15331 (Reactome)
Phosphorylated (T34) DARPP-32:PP1AArrowREACT_15496 (Reactome)
Phosphorylated (T34) DARPP-32:PP1Amim-catalysisREACT_15496 (Reactome)
PiArrowREACT_15301 (Reactome)
PiArrowREACT_15335 (Reactome)
PiArrowREACT_15438 (Reactome)
PiArrowREACT_15449 (Reactome)
PiArrowREACT_15494 (Reactome)
PiArrowREACT_15495 (Reactome)
Protein Kinase A, catalytic subunitsArrowREACT_1031 (Reactome)
Protein Kinase A, catalytic subunitsmim-catalysisREACT_15377 (Reactome)
REACT_1031 (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.
REACT_12008 (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.
REACT_12074 (Reactome) IP3 promotes the release of intracellular calcium.
REACT_1257 (Reactome) PDE4 hydrolyzes cAMP to AMP.
REACT_12602 (Reactome) Upon increase in calcium concentration, calmodulin (CaM) is activated by binding to four calcium ions.
REACT_15298 (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
REACT_15299 (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.
REACT_15301 (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.
REACT_15311 (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.
REACT_15316 (Reactome) Slow intrisinc GTPase activity results in an inactivation of the alpha-i subunit by hydrolyzing GTP to GDP.
REACT_15320 (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.
REACT_1532 (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.
REACT_15331 (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.
REACT_15332 (Reactome) The calmodulin:CaMK IV complex enters the nucleus.
REACT_15335 (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).
REACT_15336 (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.
REACT_15339 (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.
REACT_15353 (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.
REACT_15365 (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.
REACT_15377 (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.
REACT_15384 (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.
REACT_15385 (Reactome) G alpha-olf:GTP binds to inactive adenylate cyclase, causing a conformational transition in adenylate cyclase exposing the catalytic site and activating it.
REACT_15387 (Reactome) Gbetagamma rebinds Galpha-olfactory:GDP, stopping its activity
REACT_15388 (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.
REACT_15399 (Reactome) Once activated, adenylate cyclase utilizes one molecule of ATP to synthesize one molecule of cyclic AMP and pyrophosphate.
REACT_15402 (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.
REACT_15415 (Reactome) CREB readily dimerizes.
REACT_15422 (Reactome) 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 GRK2 results in inhibition of the kinase activity. This inhibition is almost completely abolished when GRK2 is phosphorylated by PKC.
REACT_15427 (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.
REACT_15435 (Reactome) The chronic activation of mu-opioid receptors, which, when coupled to pertussis toxin-sensitive Galpha-i/o proteins, inhibit adenylyl cyclase (AC).
REACT_15438 (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.
REACT_15449 (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).
REACT_15450 (Reactome) Increased Ca2+ levels, acting via calmodulin, can activate PDE which can then act upon cAMP.
REACT_15473 (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.
REACT_15491 (Reactome) The ternary complex neurotransmitter:receptor:G-protein binds GTP, resulting in activation of G protein.
REACT_15494 (Reactome) Calcineurin has been identified as a Ca2+- and calmodulin-dependent phosphoprotein phosphatase. The concentration of the enzyme is relatively high in mammalian brain.
REACT_15495 (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).
REACT_15496 (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.
REACT_15519 (Reactome) The phosphorylation of the phosphodiesterase increases its activity, forming a negative feedback loop of the cAMP signal.
REACT_15529 (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.
REACT_15534 (Reactome) 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 GRK2 kinase activity towards GPCR substrates, contributing to GPCR desensitization. Phosphorylation at Ser29, which falls within the calmodulin-binding region of GRK2, abolishes the inhibitory effect of calmodulin on GRK2 kinase activity.
REACT_15540 (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.
REACT_15547 (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.
REACT_15549 (Reactome) G proteins are inactive in the GDP-bound state. The ternary complex neurotransmitter:receptor:G-protein releases GDP.
REACT_19222 (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.
REACT_1963 (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).
REACT_23990 (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.
REACT_827 (Reactome) Phosphodiesterases (PDEs) hydrolyze cAMP and cGMP, inactivating these second messengers.
active Cam-PDE 1ArrowREACT_15450 (Reactome)
active Cam-PDE 1mim-catalysisREACT_827 (Reactome)
active PKC (alpha, gamma, delta)mim-catalysisREACT_15534 (Reactome)
cAMP:PKA regulatory subunitArrowREACT_1532 (Reactome)
p-S133-CREB1ArrowREACT_15377 (Reactome)
p-S133-CREB1ArrowREACT_15427 (Reactome)
p-S133-CREB1REACT_15415 (Reactome)
p-S29-ADRBK1(2-689)ArrowREACT_15534 (Reactome)
p-S505,S727-PLA2G4AArrowREACT_23990 (Reactome)
p-S505,S727-PLA2G4AREACT_15311 (Reactome)
p-S54-PDE4BArrowREACT_15519 (Reactome)
p-T185,Y187-MAPK1mim-catalysisREACT_23990 (Reactome)
p-T75-DARPP32s:PRKACAArrowREACT_15540 (Reactome)
p-T75-DARPP32sArrowREACT_15365 (Reactome)
p-T75-DARPP32sREACT_15438 (Reactome)
p-T75-DARPP32sREACT_15540 (Reactome)
p-T75-DARPP32sTBarREACT_15519 (Reactome)
p-T75-DARPP32smim-catalysisREACT_15540 (Reactome)
phospho-CREB dimerArrowREACT_15415 (Reactome)
phospho-CaMK IV:CalmodulinArrowREACT_15320 (Reactome)
phospho-CaMK IV:Calmodulinmim-catalysisREACT_15427 (Reactome)
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