DAG and IP3 signaling (Homo sapiens)

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6111, 12158, 922105, 1443, 4, 7cytosolendoplasmic reticulum lumennucleoplasmPDE1A ADCY4 ITPR1 phospho-CREB dimerH2OADRBK1cAMP PRKACA CALM1 ITPR3 PRKCD PRKAR2A Ca2+ I(1,4,5)P3 PKC-delta/epsilonPRKAR2A ADPITPR:I(1,4,5)P3tetramerPRKAR1B AHCYL1 PPiPDE1C DAGscAMP Ca2+ PRKACB ADCY3 AMPp-4Y-PLCG1Ca2+ I(1,4,5)P3 phospho-CaMKIV:CalmodulincAMP:PKA regulatorysubunitPRKCA active PKC (alpha,gamma, delta)ADCY5 p-S29-ADRBK1p-T566,T710,S729-PRKCE ITPR3 PI(4,5)P2H2OPRKAR2B activated PDE1dimersPRKAR1A PDE1 dimersactivated PDE1C PRKAR1A ITPR2 Protein Kinase A,catalytic subunitsPRKAR2A Phospho-PKC-delta/epsilonATPPRKAR1A PRKACG NAD+ ADCY2 ADRBK1 PRKACA Ca2+PRKACG ATPADCY1 CALM1 DNA PKA tetramerCALM1IP3 receptorhomotetramerCALM1 CAMK4CAMK4 activated PDE1A ADPPRKCG ADCY7 Mg2+ PRKAR1B Calmodulin:CaMK IVPRKAR2B cAMPPRKCE CREB1PKA tetramer:4xcAMPPRKCD ITPR2 p-S12,S13-CAMK4 Ca2+ ATPADCY8 PRKACB PRKACG PKA catalyticsubunitp-S133-CREB1Ca2+ITPR1 p-S133-CREB1 CAMK4 ADCY9 Adenylate cyclase(Mg2+ cofactor)PRKACG PRKACB p-T507,S645,S664-PRKCD(1-676) PRKAR1B PRKAR2B PRKACA Ca2+ I(1,4,5)P3PDE1B ATPADPCalmodulin:CaMK IVAHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerCALM1:4xCa2+PRKACB CALM1 CREB1PRKACA ADPATPADCY6 CALM1 ADPITPR2 activated PDE1B GRK2:calmodulinITPR3 cAMPATPITPR1 13


Description

This pathway describes the generation of DAG and IP3 by the PLCgamma-mediated hydrolysis of PIP2 and the subsequent downstream signaling events. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 1489509
Reactome-version 
Reactome version: 62
Reactome Author 
Reactome Author: Nasi, S, Annibali, D

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Bibliography

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  1. Gullingsrud J, Kim C, Taylor SS, McCammon JA.; ''Dynamic binding of PKA regulatory subunit RI alpha.''; PubMed Europe PMC Scholia
  2. Chuang TT, Paolucci L, De Blasi A.; ''Inhibition of G protein-coupled receptor kinase subtypes by Ca2+/calmodulin.''; PubMed Europe PMC Scholia
  3. 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
  4. Gu C, Cooper DM.; ''Calmodulin-binding sites on adenylyl cyclase type VIII.''; PubMed Europe PMC Scholia
  5. Patterson RL, van Rossum DB, Nikolaidis N, Gill DL, Snyder SH.; ''Phospholipase C-gamma: diverse roles in receptor-mediated calcium signaling.''; 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. 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
  8. Newton AC.; ''Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions.''; PubMed Europe PMC Scholia
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. Wang QJ.; ''PKD at the crossroads of DAG and PKC signaling.''; PubMed Europe PMC Scholia
  18. Gonzalez GA, Montminy MR.; ''Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133.''; PubMed Europe PMC Scholia
  19. 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
  20. 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
  21. 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
  22. 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
  23. 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
  24. Simpson RE, Ciruela A, Cooper DM.; ''The role of calmodulin recruitment in Ca2+ stimulation of adenylyl cyclase type 8.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114839view16:34, 25 January 2021ReactomeTeamReactome version 75
113285view11:35, 2 November 2020ReactomeTeamReactome version 74
112496view15:45, 9 October 2020ReactomeTeamReactome version 73
101408view11:29, 1 November 2018ReactomeTeamreactome version 66
100946view21:05, 31 October 2018ReactomeTeamreactome version 65
100483view19:39, 31 October 2018ReactomeTeamreactome version 64
100028view16:23, 31 October 2018ReactomeTeamreactome version 63
99581view14:55, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99203view12:43, 31 October 2018ReactomeTeamreactome version 62
93895view13:43, 16 August 2017ReactomeTeamreactome version 61
93468view11:24, 9 August 2017ReactomeTeamreactome version 61
87167view19:21, 18 July 2016MkutmonOntology Term : 'signaling pathway' added !
87166view19:21, 18 July 2016MkutmonOntology Term : 'immune response pathway' added !
86562view09:21, 11 July 2016ReactomeTeamreactome version 56
83288view10:39, 18 November 2015ReactomeTeamVersion54
81419view12:57, 21 August 2015ReactomeTeamVersion53
76890view08:16, 17 July 2014ReactomeTeamFixed remaining interactions
76595view11:57, 16 July 2014ReactomeTeamFixed remaining interactions
75926view09:58, 11 June 2014ReactomeTeamRe-fixing comment source
75628view10:50, 10 June 2014ReactomeTeamReactome 48 Update
74983view13:50, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74627view08:40, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
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)
ADRBK1 ProteinP25098 (Uniprot-TrEMBL)
ADRBK1ProteinP25098 (Uniprot-TrEMBL)
AHCYL1 ProteinO43865 (Uniprot-TrEMBL)
AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerComplexR-HSA-5226920 (Reactome)
AMPMetaboliteCHEBI:16027 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Adenylate cyclase (Mg2+ cofactor)ComplexR-HSA-170665 (Reactome)
CALM1 ProteinP0DP23 (Uniprot-TrEMBL)
CALM1:4xCa2+ComplexR-HSA-74294 (Reactome)
CALM1ProteinP0DP23 (Uniprot-TrEMBL)
CAMK4 ProteinQ16566 (Uniprot-TrEMBL)
CAMK4ProteinQ16566 (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)
DNA R-ALL-29428 (Reactome)
GRK2:calmodulinComplexR-HSA-111965 (Reactome)
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)
NAD+ MetaboliteCHEBI:15846 (ChEBI)
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)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PKA catalytic subunitComplexR-HSA-111920 (Reactome)
PKA tetramer:4xcAMPComplexR-HSA-8951729 (Reactome)
PKA tetramerComplexR-HSA-111922 (Reactome)
PKC-delta/epsilonComplexR-HSA-198276 (Reactome)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKACA ProteinP17612 (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)
PRKCE ProteinQ02156 (Uniprot-TrEMBL)
PRKCG ProteinP05129 (Uniprot-TrEMBL)
Phospho-PKC-delta/epsilonComplexR-HSA-198265 (Reactome)
Protein Kinase A, catalytic subunitsComplexR-HSA-111917 (Reactome)
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)
cAMP MetaboliteCHEBI:17489 (ChEBI)
cAMP:PKA regulatory subunitComplexR-HSA-111923 (Reactome)
cAMPMetaboliteCHEBI:17489 (ChEBI)
p-4Y-PLCG1ProteinP19174 (Uniprot-TrEMBL)
p-S12,S13-CAMK4 ProteinQ16566 (Uniprot-TrEMBL)
p-S133-CREB1 ProteinP16220 (Uniprot-TrEMBL)
p-S133-CREB1ProteinP16220 (Uniprot-TrEMBL)
p-S29-ADRBK1ProteinP25098 (Uniprot-TrEMBL)
p-T507,S645,S664-PRKCD(1-676) ProteinQ05655 (Uniprot-TrEMBL)
p-T566,T710,S729-PRKCE ProteinQ02156 (Uniprot-TrEMBL)
phospho-CREB dimerComplexR-HSA-111911 (Reactome)
phospho-CaMK IV:CalmodulinComplexR-HSA-111904 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-111912 (Reactome)
ADPArrowR-HSA-111915 (Reactome)
ADPArrowR-HSA-111919 (Reactome)
ADPArrowR-HSA-111970 (Reactome)
ADPArrowR-HSA-198314 (Reactome)
ADRBK1R-HSA-111966 (Reactome)
ADRBK1R-HSA-111970 (Reactome)
AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerTBarR-HSA-169683 (Reactome)
AMPArrowR-HSA-111955 (Reactome)
ATPR-HSA-111912 (Reactome)
ATPR-HSA-111915 (Reactome)
ATPR-HSA-111919 (Reactome)
ATPR-HSA-111930 (Reactome)
ATPR-HSA-111970 (Reactome)
ATPR-HSA-198314 (Reactome)
Adenylate cyclase (Mg2+ cofactor)mim-catalysisR-HSA-111930 (Reactome)
CALM1:4xCa2+ArrowR-HSA-111956 (Reactome)
CALM1:4xCa2+ArrowR-HSA-74448 (Reactome)
CALM1:4xCa2+R-HSA-111913 (Reactome)
CALM1R-HSA-111966 (Reactome)
CALM1R-HSA-74448 (Reactome)
CAMK4R-HSA-111913 (Reactome)
CREB1R-HSA-111912 (Reactome)
CREB1R-HSA-111919 (Reactome)
Ca2+ArrowR-HSA-169683 (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-167686 (Reactome)
DAGsArrowR-HSA-198314 (Reactome)
GRK2:calmodulinArrowR-HSA-111966 (Reactome)
H2OR-HSA-111955 (Reactome)
H2OR-HSA-167686 (Reactome)
I(1,4,5)P3ArrowR-HSA-167686 (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)
PDE1 dimersR-HSA-111956 (Reactome)
PI(4,5)P2R-HSA-167686 (Reactome)
PKA catalytic subunitArrowR-HSA-111925 (Reactome)
PKA catalytic subunitR-HSA-111924 (Reactome)
PKA tetramer:4xcAMPArrowR-HSA-8951727 (Reactome)
PKA tetramer:4xcAMPR-HSA-111925 (Reactome)
PKA tetramerR-HSA-8951727 (Reactome)
PKC-delta/epsilonR-HSA-198314 (Reactome)
PKC-delta/epsilonmim-catalysisR-HSA-198314 (Reactome)
PPiArrowR-HSA-111930 (Reactome)
Phospho-PKC-delta/epsilonArrowR-HSA-198314 (Reactome)
Protein Kinase A, catalytic subunitsArrowR-HSA-111924 (Reactome)
Protein Kinase A, catalytic subunitsmim-catalysisR-HSA-111919 (Reactome)
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-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-112282 (Reactome) The calmodulin:CaMK IV complex enters the nucleus.
R-HSA-167686 (Reactome) Inositol 1,4,5-triphosphate (IP3) is a second messenger produced by phospholipase C (PLC) metabolism of phosphoinositol 4,5-bisphosphate (PIP2) (Canossa et al. 2001).
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-198314 (Reactome) Diacylglycerol (DAG) positively regulates the autophosphorylation of protein kinase C-delta (PKC-delta), which stimulates ERK1/2 and triggers neurite outgrowth. DAG also stimulates the translocation of PKC from the cytosol to the plasma membrane. PKC-delta contributes to growth factor specificity and response to neuronal cells by promoting cell-type-specific differences in growth factor signalling. DAG can also activate PKC-epsilon in the same manner (Newton 2001).
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)
cAMP:PKA regulatory subunitArrowR-HSA-111925 (Reactome)
cAMPArrowR-HSA-111930 (Reactome)
cAMPR-HSA-111955 (Reactome)
cAMPR-HSA-8951727 (Reactome)
p-4Y-PLCG1mim-catalysisR-HSA-167686 (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)
phospho-CREB dimerArrowR-HSA-111916 (Reactome)
phospho-CaMK IV:CalmodulinArrowR-HSA-111915 (Reactome)
phospho-CaMK IV:Calmodulinmim-catalysisR-HSA-111912 (Reactome)
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