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

K05264

vasoactive intestinal peptide

K05256

corticotropin-releasing hormone

K08522

glycoprotein hormones alpha chain

K08521

lutropin subunit beta

K25483

glycoprotein hormone alpha-2

K25484

glycoprotein hormone beta-5

K05251

thyrotropin subunit beta

K05228

proopiomelanocortin

K05259

glucagon

K05258

gastric inhibitory polypeptide

K05250

follitropin subunit beta

K12334

natriuretic peptide A

K05262

pituitary adenylate cyclase-activating polypeptide

K04141

adrenergic receptor beta-1

K04142

adrenergic receptor beta-2

K04144

dopamine receptor D1

K05840

dopamine receptor D5

K04266

adenosine receptor A2a

K04160

5-hydroxytryptamine receptor 4

K04162

5-hydroxytryptamine receptor 6

K04259

prostaglandin E receptor 2

K04587

pituitary adenylate cyclase-activating polypeptide type I receptor

K04590

vasoactive intestinal peptide receptor 2

K04578

corticotropin releasing hormone receptor 1

K04579

corticotropin releasing hormone receptor 2

K04248

lutropin-choriogonadotropic hormone receptor

K04249

thyrotropin receptor

K04200

melanocortin 2 receptor

K04581

glucagon-like peptide 1 receptor

K04580

gastric inhibitory polypeptide receptor

K08424

glucose-dependent insulinotropic receptor

K04247

follicle stimulating hormone receptor

K12323

atrial natriuretic peptide receptor A [EC:4.6.1.2]

K04632

guanine nucleotide-binding protein G(s) subunit alpha

K16366

endothelin-1

K16367

endothelin-2

K05227

endothelin-3

K05237

somatostatin

K05232

neuropeptide Y

K05254

ghrelin

K05243

oxytocin-neurophysin 1

K04153

5-hydroxytryptamine receptor 1

K04129

muscarinic acetylcholine receptor M1

K04130

muscarinic acetylcholine receptor M2

K04145

dopamine receptor D2

K04615

gamma-aminobutyric acid type B receptor

K04265

adenosine receptor A1

K04197

endothelin receptor type A

K04204

neuropeptide Y receptor type 1

K04217

somatostatin receptor 1

K04218

somatostatin receptor 2

K04221

somatostatin receptor 5

K08401

hydroxycarboxylic acid receptor 1

K08402

hydroxycarboxylic acid receptor 2/3

K04328

free fatty acid receptor 2

K10042

succinate receptor 1

K04260

prostaglandin E receptor 3

K04229

oxytocin receptor

K04284

growth hormone secretagogue receptor

K04630

guanine nucleotide-binding protein G(i) subunit alpha

K08041

adenylate cyclase 1 [EC:4.6.1.1]

K08042

adenylate cyclase 2 [EC:4.6.1.1]

K08043

adenylate cyclase 3 [EC:4.6.1.1]

K08044

adenylate cyclase 4 [EC:4.6.1.1]

K08045

adenylate cyclase 5 [EC:4.6.1.1]

K08046

adenylate cyclase 6 [EC:4.6.1.1]

K08047

adenylate cyclase 7 [EC:4.6.1.1]

K08048

adenylate cyclase 8 [EC:4.6.1.1]

K08049

adenylate cyclase 9 [EC:4.6.1.1]

K11265

adenylate cyclase 10 [EC:4.6.1.1]

K04948

cyclic nucleotide gated channel alpha 1

K04949

cyclic nucleotide gated channel alpha 2

K04950

cyclic nucleotide gated channel alpha 3

K04951

cyclic nucleotide gated channel alpha 4

K04952

cyclic nucleotide gated channel beta 1

K04953

cyclic nucleotide gated channel beta 3

K02183

calmodulin

K04515

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

K05869

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

K21108

blood vessel epicardial substance

K26206

popeye domain-containing protein 2

K26207

popeye domain-containing protein 3

K04913

potassium channel subfamily K member 2

K04955

hyperpolarization activated cyclic nucleotide-gated potassium channel 2

K04957

hyperpolarization activated cyclic nucleotide-gated potassium channel 4

K05673

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

K08014

Rap guanine nucleotide exchange factor 3

K04351

Rap guanine nucleotide exchange factor 4

K07829

Ras-related protein R-Ras

K07830

Ras-related protein R-Ras2

K01115

phospholipase D1/2 [EC:3.1.4.4]

K05860

phosphatidylinositol phospholipase C, epsilon [EC:3.1.4.11]

K04440

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

K04353

Ras-related protein Rap-1A

K07836

Ras-related protein Rap-1B

K05731

T-lymphoma invasion and metastasis-inducing protein 1

K05730

guanine nucleotide exchange factor VAV

K04392

Ras-related C3 botulinum toxin substrate 1

K07860

Ras-related C3 botulinum toxin substrate 2

K07861

Ras-related C3 botulinum toxin substrate 3

K04409

p21-activated kinase 1 [EC:2.7.11.1]

K12490

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

K04513

Ras homolog gene family, member A

K05702

afadin

K00922

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

K02649

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

K04456

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

K04365

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

K04366

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

K04368

mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]

K04369

mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]

K04371

mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K04345

protein kinase A [EC:2.7.11.11]

K15494

protein phosphatase 1 regulatory subunit 1B

K06269

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

K05870

cyclic AMP-responsive element-binding protein 1

K09048

cyclic AMP-responsive element-binding protein 3

K09047

cyclic AMP-responsive element-binding protein 5

K04498

E1A/CREB-binding protein [EC:2.3.1.48]

K04355

brain-derived neurotrophic factor

K04379

proto-oncogene protein c-fos

K04448

transcription factor AP-1

K06230

zinc finger protein GLI3

K16797

zinc finger protein GLI1

K06225

patched 1

K06231

hedgehog interacting protein

K04734

NF-kappa-B inhibitor alpha

K02580

nuclear factor NF-kappa-B p105 subunit

K04735

transcription factor p65

K18435

transcription factor SOX9 (SOX group E)

K04665

anti-mullerian hormone

K07294

peroxisome proliferator-activated receptor alpha

K00232

acyl-CoA oxidase [EC:1.3.3.6]

K04446

nuclear factor of activated T-cells, cytoplasmic 1

K03914

coagulation factor II (thrombin) receptor

K02158

Bcl-2-antagonist of cell death

K07188

hormone-sensitive lipase [EC:3.1.1.79]

K04514

Rho-associated protein kinase 1 [EC:2.7.11.1]

K17388

Rho-associated protein kinase 2 [EC:2.7.11.1]

K06270

protein phosphatase 1 regulatory subunit 12A

K12755

myosin regulatory light chain 9

K12044

troponin I, cardiac muscle

K05852

phospholamban

K05853

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

K04962

ryanodine receptor 2

K05208

glutamate receptor ionotropic, NMDA 1

K05209

glutamate receptor ionotropic, NMDA 2A

K05210

glutamate receptor ionotropic, NMDA 2B

K05211

glutamate receptor ionotropic, NMDA 2C

K05212

glutamate receptor ionotropic, NMDA 2D

K05213

glutamate receptor ionotropic, NMDA 3A

K05214

glutamate receptor ionotropic, NMDA 3B

K05197

glutamate receptor 1

K05198

glutamate receptor 2

K05199

glutamate receptor 3

K05200

glutamate receptor 4

K05031

cystic fibrosis transmembrane conductance regulator [EC:5.6.1.6]

K01539

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

K01540

sodium/potassium-transporting ATPase subunit beta

K01538

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

K13360

FXYD domain-containing ion transport regulator 1

K05742

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

K16056

calcium release-activated calcium channel protein 1

K05850

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

K04850

voltage-dependent calcium channel L type alpha-1C

K04851

voltage-dependent calcium channel L type alpha-1D

K04853

voltage-dependent calcium channel L type alpha-1F

K04857

voltage-dependent calcium channel L type alpha-1S

K19021

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

K13296

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

K13293

cAMP-specific phosphodiesterase 4 [EC:3.1.4.53]

K18438

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

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

Epac: effectors and biological functions.

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

Schaub MC, Hefti MA, Zaugg M

Title

Integration of calcium with the signaling network in cardiac myocytes.

Journal

J Mol Cell Cardiol 41:183-214 (2006)
DOI:10.1016/j.yjmcc.2006.04.005

Reference

PMID:19874988

Authors

Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J

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

Saucerman JJ, McCulloch AD

Title

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

Journal

Prog Biophys Mol Biol 85:261-78 (2004)
DOI:10.1016/j.pbiomolbio.2004.01.005

Reference

PMID:21212391

Authors

Yang JH, Saucerman JJ

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

Taggart P, Boyett MR, Logantha S, Lambiase PD

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

Bozzi Y, Dunleavy M, Henshall DC

Title

Cell signaling underlying epileptic behavior.

Journal

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

Reference

PMID:10880354

Authors

Lizcano JM, Morrice N, Cohen P

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

Gerlo S, Kooijman R, Beck IM, Kolmus K, Spooren A, Haegeman G

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

Lauder JM

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

Voglis G, Tavernarakis N

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

Altarejos JY, Montminy M

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

Bozzi Y, Borrelli E

Title

The role of dopamine signaling in epileptogenesis.

Journal

Front Cell Neurosci 7:157 (2013)
DOI:10.3389/fncel.2013.00157

Reference

PMID:14715909

Authors

Ceulemans H, Bollen M

Title

Functional diversity of protein phosphatase-1, a cellular economizer and reset button.

Journal

Physiol Rev 84:1-39 (2004)
DOI:10.1152/physrev.00013.2003

Reference

PMID:16571352

Authors

Lipinski RJ, Gipp JJ, Zhang J, Doles JD, Bushman W

Title

Unique and complimentary activities of the Gli transcription factors in Hedgehog signaling.

Journal

Exp Cell Res 312:1925-38 (2006)
DOI:10.1016/j.yexcr.2006.02.019

Reference

PMID:21693691

Authors

Lasala C, Schteingart HF, Arouche N, Bedecarras P, Grinspon RP, Picard JY, Josso N, di Clemente N, Rey RA

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)
DOI:10.1152/ajpendo.00187.2011

Reference

PMID:19460777

Authors

Rosenkranz AC, Rauch BH, Freidel K, Schror K

Title

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

Journal

Cardiovasc Res 83:778-84 (2009)
DOI:10.1093/cvr/cvp163

Reference

PMID:11117527