KEGG   PATHWAY: map04020Help
Entry
map04020                    Pathway                                

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
BRITE hierarchy
Pathway map
Calcium signaling pathway
map04020

All organismsOrtholog table
Disease
H00441  
Progressive osseous heteroplasia (POH)
H00608  
46,XY disorders of sex development (Disorders in androgen synthesis or action)
H00627  
Premature ovarian failure
H00699  
Central core disease
H00715  
Darier disease
H00728  
Brugada syndrome (BRS)
H00746  
Hypokalemic periodic paralysis (HypoPP)
H00749  
Episodic ataxias
H00755  
Acrokeratosis verruciformis
H00759  
Waardenburg syndrome (WS)
H00775  
Familial or sporadic hemiplegic migraine
H00787  
Congenital stationary night blindness (CSNB)
H00801  
Familial thoracic aortic aneurysm and dissection (TAAD)
H00823  
ABCD syndrome
H00865  
Lethal congenital contractural syndrome (LCCS)
H00910  
Hirschsprung disease (HD)
H00937  
Precocious puberty
H01019  
Catecholaminergic polymorphic ventricular tachycardia
H01118  
Progressive external ophthalmoplegia (PEO)
H01129  
Brody myopathy
H01307  
Nonsyndromic congenital nail disorder (NDNC)
H01310  
Multi-minicore disease (MmD)
Other DBs
GO: 
Reference
  Authors
Berridge MJ, Bootman MD, Roderick HL.
  Title
Calcium signalling: dynamics, homeostasis and remodelling.
  Journal
Nat Rev Mol Cell Biol 4:517-29 (2003)
Reference
  Authors
Berridge MJ, Lipp P, Bootman MD.
  Title
The versatility and universality of calcium signalling.
  Journal
Nat Rev Mol Cell Biol 1:11-21 (2000)
Reference
  Authors
Wang MC, Dolphin A, Kitmitto A.
  Title
L-type voltage-gated calcium channels: understanding function through structure.
  Journal
FEBS Lett 564:245-50 (2004)
Reference
  Authors
Ferrier GR, Howlett SE.
  Title
Cardiac excitation-contraction coupling: role of membrane potential in regulation of contraction.
  Journal
Am J Physiol Heart Circ Physiol 280:H1928-44 (2001)
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
Am J Physiol Cell Physiol 281:C1743-56 (2001)
Reference
PMID:8125957
  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
J Bioenerg Biomembr 35:577-98 (2003)
Reference
PMID:9149541
  Authors
Yakel JL.
  Title
Calcineurin regulation of synaptic function: from ion channels to transmitter release and gene transcription.
  Journal
Trends Pharmacol Sci 18:124-34 (1997)
Reference
  Authors
Fukunaga K, Miyamoto E.
  Title
A working model of CaM kinase II activity in hippocampal long-term potentiation and memory.
  Journal
Neurosci Res 38:3-17 (2000)
Reference
PMID:9235901
  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
J Biol Chem 272:19125-32 (1997)
Reference
PMID:7861177
  Authors
Furuichi T, Mikoshiba K.
  Title
Inositol 1, 4, 5-trisphosphate receptor-mediated Ca2+ signaling in the brain.
  Journal
J Neurochem 64:953-60 (1995)
Reference
  Authors
Bruce JI, Straub SV, Yule DI.
  Title
Crosstalk between cAMP and Ca2+ signaling in non-excitable cells.
  Journal
Cell Calcium 34:431-44 (2003)
Reference
  Authors
Lee HC, Munshi C, Graeff R.
  Title
Structures and activities of cyclic ADP-ribose, NAADP and their metabolic enzymes.
  Journal
Mol Cell Biochem 193:89-98 (1999)
Reference
  Authors
Crompton M.
  Title
Mitochondrial intermembrane junctional complexes and their role in cell death.
  Journal
J Physiol 529 Pt 1:11-21 (2000)
Reference
  Authors
Grewal SS, York RD, Stork PJ.
  Title
Extracellular-signal-regulated kinase signalling in neurons.
  Journal
Curr Opin Neurobiol 9:544-53 (1999)
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
Mol Cell Biol 23:7068-81 (2003)
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
Mol Biol Cell 14:4003-14 (2003)
Reference
  Authors
Tornquist K
  Title
Sphingosine 1-phosphate, sphingosine kinase and autocrine calcium signalling in thyroid cells.
  Journal
Acta Physiol (Oxf) 204:151-7 (2012)
Reference
  Authors
Feske S
  Title
Immunodeficiency due to defects in store-operated calcium entry.
  Journal
Ann N Y Acad Sci 1238:74-90 (2011)
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
Braz J Med Biol Res 44:1080-7 (2011)
Reference
  Authors
Baba Y, Kurosaki T
  Title
[Regulation of store-operated calcium entry by STIM1].
  Journal
Seikagaku 80:1123-8 (2008)
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