Entry
Name
Calcium signaling pathway
Description
Ca2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this external source of signal Ca2+ by activating various entry channels with widely different properties. The voltage-operated channels (VOCs) are found in excitable cells and generate the rapid Ca2+ fluxes that control fast cellular processes. There are many other Ca2+-entry channels, such as the receptor-operated channels (ROCs), for example the NMDA (N-methyl-D-aspartate) receptors (NMDARs) that respond to glutamate. There also are second-messenger-operated channels (SMOCs) and store-operated channels (SOCs).
The other principal source of Ca2+ for signalling is the internal stores that are located primarily in the endoplasmic/sarcoplasmic reticulum (ER/SR), in which inositol-1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RYRs) regulate the release of Ca2+. The principal activator of these channels is Ca2+ itself and this process of Ca2+-induced Ca2+ release is central to the mechanism of Ca2+ signalling. Various second messengers or modulators also control the release of Ca2+. IP3, which is generated by pathways using different isoforms of phospholipase C (PLCbeta, delta, epsilon, gamma and zeta), regulates the IP3Rs. Cyclic ADP-ribose (cADPR) releases Ca2+ via RYRs. Nicotinic acid adenine dinucleotide phosphate (NAADP) may activate a distinct Ca2+ release mechanism on separate acidic Ca2+ stores. Ca2+ release via the NAADP-sensitive mechanism may also feedback onto either RYRs or IP3Rs. cADPR and NAADP are generated by CD38. This enzyme might be sensitive to the cellular metabolism, as ATP and NADH inhibit it.
The influx of Ca2+ from the environment or release from internal stores causes a very rapid and dramatic increase in cytoplasmic calcium concentration, which has been widely exploited for signal transduction. Some proteins, such as troponin C (TnC) involved in muscle contraction, directly bind to and sense Ca2+. However, in other cases Ca2+ is sensed through intermediate calcium sensors such as calmodulin (CALM).
Class
Environmental Information Processing; Signal transduction
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Orthology
K05849 solute carrier family 8 (sodium/calcium exchanger)
K04129 muscarinic acetylcholine receptor M1
K04131 muscarinic acetylcholine receptor M3
K04133 muscarinic acetylcholine receptor M5
K04141 adrenergic receptor beta-1
K04142 adrenergic receptor beta-2
K04143 adrenergic receptor beta-3
K04160 5-hydroxytryptamine receptor 4
K04161 5-hydroxytryptamine receptor 5
K04162 5-hydroxytryptamine receptor 6
K04163 5-hydroxytryptamine receptor 7
K04632 guanine nucleotide-binding protein G(s) subunit alpha
K04633 guanine nucleotide-binding protein G(olf) subunit alpha
K23450 sarcoplasmic reticulum histidine-rich calcium-binding protein
K16059 stromal interaction molecule 1
K18196 stromal interaction molecule 2
K16056 calcium release-activated calcium channel protein 1
K16057 calcium release-activated calcium channel protein 2
K16058 calcium release-activated calcium channel protein 3
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
K04344 voltage-dependent calcium channel P/Q type alpha-1A
K04849 voltage-dependent calcium channel N type alpha-1B
K04852 voltage-dependent calcium channel R type alpha-1E
K04854 voltage-dependent calcium channel T type alpha-1G
K04855 voltage-dependent calcium channel T type alpha-1H
K04856 voltage-dependent calcium channel T type alpha-1I
K04809 nicotinic acetylcholine receptor alpha-7
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
K04322 cysteinyl leukotriene receptor 1
K04323 cysteinyl leukotriene receptor 2
K04130 muscarinic acetylcholine receptor M2
K04135 adrenergic receptor alpha-1A
K04136 adrenergic receptor alpha-1B
K04137 adrenergic receptor alpha-1D
K04166 angiotensin II receptor type 1
K04197 endothelin receptor type A
K04198 endothelin receptor type B
K03914 coagulation factor II (thrombin) receptor
K04603 metabotropic glutamate receptor 1
K04604 metabotropic glutamate receptor 5
K04169 gastrin-releasing peptide receptor
K04157 5-hydroxytryptamine receptor 2
K04248 lutropin-choriogonadotropic hormone receptor
K04226 arginine vasopressin receptor 1A
K04227 arginine vasopressin receptor 1B
K04297 leukotriene B4 receptor 2
K04279 platelet-activating factor receptor
K04258 prostaglandin E receptor 1
K04260 prostaglandin E receptor 3
K04262 prostaglandin F receptor
K04264 thromboxane A2 receptor
K04282 thyrotropin-releasing hormone receptor
K04194 cholecystokinin A receptor
K04195 cholecystokinin B receptor
K04189 C-X-C chemokine receptor type 4
K04634 guanine nucleotide-binding protein G(q) subunit alpha
K04635 guanine nucleotide-binding protein subunit alpha-11
K04636 guanine nucleotide-binding protein subunit alpha-14
K04637 guanine nucleotide-binding protein subunit alpha-15
K04357 epidermal growth factor
K08774 transforming growth factor, alpha
K04359 platelet-derived growth factor subunit A
K17386 platelet-derived growth factor subunit B
K05450 platelet derived growth factor C/D
K18496 fibroblast growth factor 1
K18497 fibroblast growth factor 2
K04358 fibroblast growth factor
K22603 fibroblast growth factor 19
K22429 fibroblast growth factor 21
K22428 fibroblast growth factor 23
K05448 vascular endothelial growth factor A
K16858 vascular endothelial growth factor B
K05449 vascular endothelial growth factor C/D
K05451 nerve growth factor, alpha
K02582 nerve growth factor, beta
K05460 hepatocyte growth factor
K23441 hepatocyte growth factor-like protein
K05452 glial cell derived neurotrophic factor
K10784 T cell receptor alpha chain V region
K10785 T-cell receptor beta chain V region
K06856 immunoglobulin heavy chain
K04958 inositol 1,4,5-triphosphate receptor type 1
K04959 inositol 1,4,5-triphosphate receptor type 2
K04960 inositol 1,4,5-triphosphate receptor type 3
K16896 two pore calcium channel protein 1
K14077 two pore calcium channel protein 2
K20858 calcium uniporter protein, mitochondrial
K05862 voltage-dependent anion channel protein 1
K15040 voltage-dependent anion channel protein 2
K15041 voltage-dependent anion channel protein 3
K05863 solute carrier family 25 (mitochondrial adenine nucleotide translocator), member 4/5/6/31
K05865 troponin C, slow skeletal and cardiac muscles
K12042 troponin C, skeletal muscle
K07190 phosphorylase kinase alpha/beta subunit
K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K06268 serine/threonine-protein phosphatase 2B regulatory subunit
K15590 transcription factor EB
K04446 nuclear factor of activated T-cells, cytoplasmic 1
K17332 nuclear factor of activated T-cells, cytoplasmic 2
K17333 nuclear factor of activated T-cells, cytoplasmic 3
K17334 nuclear factor of activated T-cells, cytoplasmic 4
K13755 calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase [EC:3.1.4.17 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C06124 Sphingosine 1-phosphate
C11556 1-Phosphatidyl-1D-myo-inositol 3,5-bisphosphate
C13051 Nicotinic acid adenine dinucleotide phosphate
Reference
Authors
Berridge MJ, Bootman MD, Roderick HL.
Title
Calcium signalling: dynamics, homeostasis and remodelling.
Journal
Reference
Authors
Berridge MJ, Lipp P, Bootman MD.
Title
The versatility and universality of calcium signalling.
Journal
Reference
Authors
Wang MC, Dolphin A, Kitmitto A.
Title
L-type voltage-gated calcium channels: understanding function through structure.
Journal
Reference
Authors
Ferrier GR, Howlett SE.
Title
Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction.
Journal
Reference
Authors
Keef KD, Hume JR, Zhong J.
Title
Regulation of cardiac and smooth muscle Ca(2+) channels (Ca(V)1.2a,b) by protein kinases.
Journal
Reference
Authors
Hell JW, Appleyard SM, Yokoyama CT, Warner C, Catterall WA.
Title
Differential phosphorylation of two size forms of the N-type calcium channel alpha 1 subunit which have different COOH termini.
Journal
J Biol Chem 269:7390-6 (1994)
Reference
Authors
Yunker AM.
Title
Modulation and pharmacology of low voltage-activated ("T-Type") calcium channels.
Journal
Reference
Authors
Yakel JL.
Title
Calcineurin regulation of synaptic function: from ion channels to transmitter release and gene transcription.
Journal
Reference
Authors
Fukunaga K, Miyamoto E.
Title
A working model of CaM kinase II activity in hippocampal long-term potentiation and memory.
Journal
Reference
Authors
Della Rocca GJ, van Biesen T, Daaka Y, Luttrell DK, Luttrell LM, Lefkowitz RJ.
Title
Ras-dependent mitogen-activated protein kinase activation by G protein-coupled receptors. Convergence of Gi- and Gq-mediated pathways on calcium/calmodulin, Pyk2, and Src kinase.
Journal
Reference
Authors
Furuichi T, Mikoshiba K.
Title
Inositol 1, 4, 5-trisphosphate receptor-mediated Ca2+ signaling in the brain.
Journal
Reference
Authors
Bruce JI, Straub SV, Yule DI.
Title
Crosstalk between cAMP and Ca2+ signaling in non-excitable cells.
Journal
Reference
Authors
Lee HC, Munshi C, Graeff R.
Title
Structures and activities of cyclic ADP-ribose, NAADP and their metabolic enzymes.
Journal
Reference
Authors
Crompton M.
Title
Mitochondrial intermembrane junctional complexes and their role in cell death.
Journal
Reference
Authors
Grewal SS, York RD, Stork PJ.
Title
Extracellular-signal-regulated kinase signalling in neurons.
Journal
Reference
Authors
Trushin SA, Pennington KN, Carmona EM, Asin S, Savoy DN, Billadeau DD, Paya CV.
Title
Protein kinase Calpha (PKCalpha) acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T lymphocytes.
Journal
Reference
Authors
Hutchins JR, Dikovskaya D, Clarke PR.
Title
Regulation of Cdc2/cyclin B activation in Xenopus egg extracts via inhibitory phosphorylation of Cdc25C phosphatase by Ca(2+)/calmodulin-dependent protein [corrected] kinase II.
Journal
Reference
Authors
Tornquist K
Title
Sphingosine 1-phosphate, sphingosine kinase and autocrine calcium signalling in thyroid cells.
Journal
Reference
Authors
Feske S
Title
Immunodeficiency due to defects in store-operated calcium entry.
Journal
Reference
Authors
Giachini FR, Lima VV, Hannan JL, Carneiro FS, Webb RC, Tostes RC
Title
STIM1/Orai1-mediated store-operated Ca2+ entry: the tip of the iceberg.
Journal
Reference
Authors
Baba Y, Kurosaki T
Title
[Regulation of store-operated calcium entry by STIM1].
Journal
Seikagaku 80:1123-8 (2008)
Reference
Authors
Galione A, Evans AM, Ma J, Parrington J, Arredouani A, Cheng X, Zhu MX
Title
The acid test: the discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca(2+) release channels.
Journal
Reference
Authors
Beard NA, Wei L, Dulhunty AF
Title
Ca(2+) signaling in striated muscle: the elusive roles of triadin, junctin, and calsequestrin.
Journal
Reference
Authors
Marty I
Title
Triadin regulation of the ryanodine receptor complex.
Journal
Reference
Authors
Arvanitis DA, Vafiadaki E, Sanoudou D, Kranias EG
Title
Histidine-rich calcium binding protein: the new regulator of sarcoplasmic reticulum calcium cycling.
Journal
Related pathway
ko04070 Phosphatidylinositol signaling system
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