KEGG PATHWAY: ko04024

PATHWAY: ko04024

Entry

ko04024                     Pathway

Name

cAMP signaling pathway

Description

cAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands including hormones, neurotransmitters, and other signaling molecules. cAMP regulates pivotal physiologic processes including metabolism, secretion, calcium homeostasis, muscle contraction, cell fate, and gene transcription. cAMP acts directly on three main targets: protein kinase A (PKA), the exchange protein activated by cAMP (Epac), and cyclic nucleotide-gated ion channels (CNGCs). PKA modulates, via phosphorylation, a number of cellular substrates, including transcription factors, ion channels, transporters, exchangers, intracellular Ca2+ -handling proteins, and the contractile machinery. Epac proteins function as guanine nucleotide exchange factors (GEFs) for both Rap1 and Rap2. Various effector proteins, including adaptor proteins implicated in modulation of the actin cytoskeleton, regulators of G proteins of the Rho family, and phospholipases, relay signaling downstream from Rap.

Class

Environmental Information Processing; Signal transduction

Pathway map

ko04024

cAMP signaling pathway

Other DBs

GO:

0019933

Orthology

K00232

E1.3.3.6, ACOX1, ACOX3; acyl-CoA oxidase [EC:1.3.3.6]

K00922

PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]

K01115

PLD1_2; phospholipase D1/2 [EC:3.1.4.4]

K01538

FXYD2, ATP1G1; sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)

K01539

ATP1A; sodium/potassium-transporting ATPase subunit alpha [EC:7.2.2.13]

K01540

ATP1B, CD298; sodium/potassium-transporting ATPase subunit beta

K02158

BAD; Bcl-2-antagonist of cell death

K02183

CALM; calmodulin

K02580

NFKB1; nuclear factor NF-kappa-B p105 subunit

K02649

PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta

K03914

F2R, PAR1; coagulation factor II (thrombin) receptor

K04129

CHRM1; muscarinic acetylcholine receptor M1

K04130

CHRM2; muscarinic acetylcholine receptor M2

K04141

ADRB1; adrenergic receptor beta-1

K04142

ADRB2; adrenergic receptor beta-2

K04144

DRD1; dopamine receptor D1

K04145

DRD2; dopamine receptor D2

K04153

HTR1; 5-hydroxytryptamine receptor 1

K04160

HTR4; 5-hydroxytryptamine receptor 4

K04162

HTR6; 5-hydroxytryptamine receptor 6

K04197

EDNRA; endothelin receptor type A

K04200

MC2R; melanocortin 2 receptor

K04204

NPY1R; neuropeptide Y receptor type 1

K04217

SSTR1; somatostatin receptor 1

K04218

SSTR2; somatostatin receptor 2

K04221

SSTR5; somatostatin receptor 5

K04229

OXTR; oxytocin receptor

K04247

FSHR; follicle stimulating hormone receptor

K04248

LHCGR; lutropin-choriogonadotropic hormone receptor

K04249

TSHR; thyrotropin receptor

K04259

PTGER2; prostaglandin E receptor 2

K04260

PTGER3; prostaglandin E receptor 3

K04265

ADORA1; adenosine receptor A1

K04266

ADORA2A, ADOR; adenosine receptor A2a

K04284

GHSR; growth hormone secretagogue receptor

K04328

FFAR2, GPR43; free fatty acid receptor 2

K04345

PKA; protein kinase A [EC:2.7.11.11]

K04351

RAPGEF4, EPAC2; Rap guanine nucleotide exchange factor 4

K04353

RAP1A; Ras-related protein Rap-1A

K04355

BDNF; brain-derived neurotrophic factor

K04365

BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04366

RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04368

MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]

K04369

MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]

K04371

ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K04379

FOS; proto-oncogene protein c-fos

K04392

RAC1; Ras-related C3 botulinum toxin substrate 1

K04409

PAK1; p21-activated kinase 1 [EC:2.7.11.1]

K04440

JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]

K04446

NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1

K04448

JUN; transcription factor AP-1

K04456

AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]

K04498

EP300, CREBBP, KAT3; E1A/CREB-binding protein [EC:2.3.1.48]

K04513

RHOA; Ras homolog gene family, member A

K04514

ROCK1; Rho-associated protein kinase 1 [EC:2.7.11.39]

K04515

CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]

K04578

CRHR1; corticotropin releasing hormone receptor 1

K04579

CRHR2; corticotropin releasing hormone receptor 2

K04580

GIPR; gastric inhibitory polypeptide receptor

K04581

GLP1R; glucagon-like peptide 1 receptor

K04587

ADCYAP1R1, PACAPRI; pituitary adenylate cyclase-activating polypeptide type I receptor

K04590

VIPR2; vasoactive intestinal peptide receptor 2

K04615

GABBR; gamma-aminobutyric acid type B receptor

K04630

GNAI; guanine nucleotide-binding protein G(i) subunit alpha

K04632

GNAS; guanine nucleotide-binding protein G(s) subunit alpha

K04665

AMH; anti-mullerian hormone

K04734

NFKBIA; NF-kappa-B inhibitor alpha

K04735

RELA; transcription factor p65

K04850

CACNA1C, CAV1.2; voltage-dependent calcium channel L type alpha-1C

K04851

CACNA1D, CAV1.3; voltage-dependent calcium channel L type alpha-1D

K04853

CACNA1F, CAV1.4; voltage-dependent calcium channel L type alpha-1F

K04857

CACNA1S, CAV1.1; voltage-dependent calcium channel L type alpha-1S

K04913

KCNK2, K2P2.1; potassium channel subfamily K member 2

K04948

CNGA1; cyclic nucleotide gated channel alpha 1

K04949

CNGA2; cyclic nucleotide gated channel alpha 2

K04950

CNGA3; cyclic nucleotide gated channel alpha 3

K04951

CNGA4; cyclic nucleotide gated channel alpha 4

K04952

CNGB1; cyclic nucleotide gated channel beta 1

K04953

CNGB3; cyclic nucleotide gated channel beta 3

K04955

HCN2; hyperpolarization activated cyclic nucleotide-gated potassium channel 2

K04957

HCN4; hyperpolarization activated cyclic nucleotide-gated potassium channel 4

K04962

RYR2; ryanodine receptor 2

K05031

CFTR, ABCC7; cystic fibrosis transmembrane conductance regulator [EC:5.6.1.6]

K05197

GRIA1; glutamate receptor 1

K05198

GRIA2; glutamate receptor 2

K05199

GRIA3; glutamate receptor 3

K05200

GRIA4; glutamate receptor 4

K05208

GRIN1; glutamate receptor ionotropic, NMDA 1

K05209

GRIN2A; glutamate receptor ionotropic, NMDA 2A

K05210

GRIN2B; glutamate receptor ionotropic, NMDA 2B

K05211

GRIN2C; glutamate receptor ionotropic, NMDA 2C

K05212

GRIN2D; glutamate receptor ionotropic, NMDA 2D

K05213

GRIN3A; glutamate receptor ionotropic, NMDA 3A

K05214

GRIN3B; glutamate receptor ionotropic, NMDA 3B

K05227

EDN3; endothelin-3

K05228

POMC; proopiomelanocortin

K05232

NPY; neuropeptide Y

K05237

SST; somatostatin

K05243

OXT; oxytocin-neurophysin 1

K05250

FSHB; follitropin subunit beta

K05251

TSHB; thyrotropin subunit beta

K05254

GHRL; ghrelin

K05256

CRH; corticotropin-releasing hormone

K05258

GIP; gastric inhibitory polypeptide

K05259

GCG; glucagon

K05262

ADCYAP; pituitary adenylate cyclase-activating polypeptide

K05264

VIP; vasoactive intestinal peptide

K05673

ABCC4; ATP-binding cassette, subfamily C (CFTR/MRP), member 4

K05702

AF6, MLLT4; afadin

K05730

VAV; guanine nucleotide exchange factor VAV

K05731

TIAM1; T-lymphoma invasion and metastasis-inducing protein 1

K05742

SLC9A1, NHE1; solute carrier family 9 (sodium/hydrogen exchanger), member 1

K05840

DRD5; dopamine receptor D5

K05850

ATP2B; P-type Ca2+ transporter type 2B [EC:7.2.2.10]

K05852

PLN; phospholamban

K05853

ATP2A; P-type Ca2+ transporter type 2A [EC:7.2.2.10]

K05860

PLCE; phosphatidylinositol phospholipase C, epsilon [EC:3.1.4.11]

K05869

CAMK4; calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17]

K05870

CREB1; cyclic AMP-responsive element-binding protein 1

K06225

PTCH1; patched 1

K06230

GLI3; zinc finger protein GLI3

K06231

HHIP; hedgehog interacting protein

K06269

PPP1C; serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]

K06270

PPP1R12A, MYPT1; protein phosphatase 1 regulatory subunit 12A

K07188

LIPE, HSL; hormone-sensitive lipase [EC:3.1.1.79]

K07294

NR1C1, PPARA; peroxisome proliferator-activated receptor alpha

K07829

RRAS; Ras-related protein R-Ras

K07830

RRAS2, TC21; Ras-related protein R-Ras2

K07836

RAP1B; Ras-related protein Rap-1B

K07860

RAC2; Ras-related C3 botulinum toxin substrate 2

K07861

RAC3; Ras-related C3 botulinum toxin substrate 3

K08014

RAPGEF3, EPAC1; Rap guanine nucleotide exchange factor 3

K08041

ADCY1; adenylate cyclase 1 [EC:4.6.1.1]

K08042

ADCY2; adenylate cyclase 2 [EC:4.6.1.1]

K08043

ADCY3; adenylate cyclase 3 [EC:4.6.1.1]

K08044

ADCY4; adenylate cyclase 4 [EC:4.6.1.1]

K08045

ADCY5; adenylate cyclase 5 [EC:4.6.1.1]

K08046

ADCY6; adenylate cyclase 6 [EC:4.6.1.1]

K08047

ADCY7; adenylate cyclase 7 [EC:4.6.1.1]

K08048

ADCY8; adenylate cyclase 8 [EC:4.6.1.1]

K08049

ADCY9; adenylate cyclase 9 [EC:4.6.1.1]

K08401

HCAR1, GPR81; hydroxycarboxylic acid receptor 1

K08402

HCAR2_3, GPR109; hydroxycarboxylic acid receptor 2/3

K08424

GPR119; glucose-dependent insulinotropic receptor

K08521

LHB; lutropin subunit beta

K08522

CGA; glycoprotein hormones alpha chain

K09047

CREB5, CREBPA; cyclic AMP-responsive element-binding protein 5

K09048

CREB3; cyclic AMP-responsive element-binding protein 3

K10042

SUCNR1, GPR91; succinate receptor 1

K11265

ADCY10; adenylate cyclase 10 [EC:4.6.1.1]

K12044

TNNI3; troponin I, cardiac muscle

K12323

ANPRA, NPR1; atrial natriuretic peptide receptor A [EC:4.6.1.2]

K12334

NPPA; natriuretic peptide A

K12490

ARAP3; Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3

K12755

MYL9; myosin regulatory light chain 9

K13293

PDE4; cAMP-specific phosphodiesterase 4 [EC:3.1.4.53]

K13296

PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [EC:3.1.4.17]

K13360

FXYD1, PLM; FXYD domain-containing ion transport regulator 1

K15494

PPP1R1B, DARPP32; protein phosphatase 1 regulatory subunit 1B

K16056

ORAI1; calcium release-activated calcium channel protein 1

K16366

EDN1; endothelin-1

K16367

EDN2; endothelin-2

K16797

GLI1; zinc finger protein GLI1

K17388

ROCK2; Rho-associated protein kinase 2 [EC:2.7.11.39]

K18435

SOX9; transcription factor SOX9 (SOX group E)

K18438

PDE10; cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10 [EC:3.1.4.17 3.1.4.35]

K19021

PDE3A; cGMP-inhibited 3',5'-cyclic phosphodiesterase A [EC:3.1.4.17]

K21108

BVES, POPDC1; blood vessel epicardial substance

K25483

GPHA2; glycoprotein hormone alpha-2

K25484

GPHB5; glycoprotein hormone beta-5

K26206

POPDC2; popeye domain-containing protein 2

K26207

POPDC3; popeye domain-containing protein 3

Compound

C00020

AMP

C00042

Succinate

C00076

Calcium cation

C00080

H+

C00165

Diacylglycerol

C00186

(S)-Lactate

C00212

Adenosine

C00238

Potassium cation

C00288

HCO3-

C00334

4-Aminobutanoate

C00416

Phosphatidate

C00547

L-Noradrenaline

C00575

3',5'-Cyclic AMP

C00584

Prostaglandin E2

C00698

Cl-

C00780

Serotonin

C00788

L-Adrenaline

C01089

(R)-3-Hydroxybutanoate

C01245

D-myo-Inositol 1,4,5-trisphosphate

C01312

Prostaglandin I2

C01330

Sodium cation

C01996

Acetylcholine

C03758

Dopamine

C20792

Oleoylethanolamide

C20793

3-Hydroxyoctanoate

Reference

PMID:11493633

Authors

Fimia GM, Sassone-Corsi P

Title

Cyclic AMP signalling.

Journal

J Cell Sci 114:1971-2 (2001)

Reference

PMID:18323530

Authors

Serezani CH, Ballinger MN, Aronoff DM, Peters-Golden M

Title

Cyclic AMP: master regulator of innate immune cell function.

Journal

Am J Respir Cell Mol Biol 39:127-32 (2008)
DOI:10.1165/rcmb.2008-0091TR

Reference

PMID:24281338

Authors

Oldenburger A, Maarsingh H, Schmidt M

Title

Multiple facets of cAMP signalling and physiological impact: cAMP compartmentalization in the lung.

Journal

Pharmaceuticals (Basel) 5:1291-331 (2012)
DOI:10.3390/ph5121291

Reference

PMID:24613710

Authors

Ahuja M, Jha A, Maleth J, Park S, Muallem S

Title

cAMP and Ca signaling in secretory epithelia: Crosstalk and synergism.

Journal

Cell Calcium 55:385-393 (2014)
DOI:10.1016/j.ceca.2014.01.006

Reference

PMID:22082266

Authors

Shirshev SV

Title

Role of Epac proteins in mechanisms of cAMP-dependent immunoregulation.

Journal

Biochemistry (Mosc) 76:981-98 (2011)
DOI:10.1134/S000629791109001X

Reference

PMID:18176800

Authors

Roscioni SS, Elzinga CR, Schmidt M

Title

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Journal

Naunyn Schmiedebergs Arch Pharmacol 377:345-57 (2008)
DOI:10.1007/s00210-007-0246-7

Reference

PMID:24450633

Authors

Roberts OL, Dart C

Title

cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP).

Journal

Biochem Soc Trans 42:89-97 (2014)
DOI:10.1042/BST20130253

Reference

PMID:16765984

Authors

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Title

Integration of calcium with the signaling network in cardiac myocytes.

Journal

J Mol Cell Cardiol 41:183-214 (2006)
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Reference

PMID:19874988

Authors

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Title

The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications.

Journal

J Am Coll Cardiol 54:1747-62 (2009)
DOI:10.1016/j.jacc.2009.05.015

Reference

PMID:15142747

Authors

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Title

Mechanistic systems models of cell signaling networks: a case study of myocyte adrenergic regulation.

Journal

Prog Biophys Mol Biol 85:261-78 (2004)
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Reference

PMID:21212391

Authors

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Title

Computational models reduce complexity and accelerate insight into cardiac signaling networks.

Journal

Circ Res 108:85-97 (2011)
DOI:10.1161/CIRCRESAHA.110.223602

Reference

PMID:22022314

Authors

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Title

Anger, emotion, and arrhythmias: from brain to heart.

Journal

Front Physiol 2:67 (2011)
DOI:10.3389/fphys.2011.00067

Reference

PMID:21852968

Authors

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Title

Cell signaling underlying epileptic behavior.

Journal

Front Behav Neurosci 5:45 (2011)
DOI:10.3389/fnbeh.2011.00045

Reference

PMID:10880354

Authors

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Title

Regulation of BAD by cAMP-dependent protein kinase is mediated via phosphorylation of a novel site, Ser155.

Journal

Biochem J 349:547-57 (2000)
DOI:10.1042/bj3490547

Reference

PMID:21744067

Authors

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Title

Cyclic AMP: a selective modulator of NF-kappaB action.

Journal

Cell Mol Life Sci 68:3823-41 (2011)
DOI:10.1007/s00018-011-0757-8

Reference

PMID:7688165

Authors

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Title

Neurotransmitters as growth regulatory signals: role of receptors and second messengers.

Journal

Trends Neurosci 16:233-40 (1993)
DOI:10.1016/0166-2236(93)90162-F

Reference

PMID:17077866

Authors

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Title

The role of synaptic ion channels in synaptic plasticity.

Journal

EMBO Rep 7:1104-10 (2006)
DOI:10.1038/sj.embor.7400830

Reference

PMID:21346730

Authors

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Title

CREB and the CRTC co-activators: sensors for hormonal and metabolic signals.

Journal

Nat Rev Mol Cell Biol 12:141-51 (2011)
DOI:10.1038/nrm3072

Reference

PMID:24062645

Authors

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Title

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Journal

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Reference

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Authors

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Title

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Journal

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Reference

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Authors

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Title

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Reference

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Authors

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Title

SOX9 and SF1 are involved in cyclic AMP-mediated upregulation of anti-Mullerian gene expression in the testicular prepubertal Sertoli cell line SMAT1.

Journal

Am J Physiol Endocrinol Metab 301:E539-47 (2011)
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Reference

PMID:19460777

Authors

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Title

Regulation of protease-activated receptor-1 by vasodilatory prostaglandins via NFAT.

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Reference

PMID:11117527