Reactome | Activation of Calcineurin

Activation of Calcineurin

Stable Identifier

R-HSA-2730872

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Immune System (Homo sapiens)

- Innate Immune System (Homo sapiens)
  - C-type lectin receptors (CLRs) (Homo sapiens)
    - CLEC7A (Dectin-1) signaling (Homo sapiens)
      - CLEC7A (Dectin-1) induces NFAT activation (Homo sapiens)
        
        Activation of Calcineurin (Homo sapiens)
  - Fc epsilon receptor (FCERI) signaling (Homo sapiens)
    - FCERI mediated Ca+2 mobilization (Homo sapiens)
      - Activation of Calcineurin (Homo sapiens)

General

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Calcineurin (CaN), also called protein phosphatase 2B (PP2B), is a calcium/Calmodulin (CaM)-dependent serine/threonine protein phosphatase. It exists as a heterodimer consisting of CaM-binding catalytic subunit CaN A chain and a Ca+2 binding regulatory CaN B chain. At low calcium concentrations, CaN exists in an inactive state, where the autoinhibitory domain (AID) binds to the active-site cleft. Upon an increase in calcium concentration CaM binds to Ca+2 ions and gets activated. Active CaM binds to CaN regulatory domain (RD) and this causes release of the AID and activation of the phosphatase (Rumi-Masante et al. 2012). Binding of calcium to CaN B regulatory chain also causes a conformational change of the RD of CaN A chain (Yang & Klee 2000).

Literature References

PubMed ID	Title	Journal	Year
11015619	Calcineurin: form and function Rusnak, F, Mertz, P	Physiol. Rev.	2000
18296442	The secondary structure of calcineurin regulatory region and conformational change induced by calcium/calmodulin binding Kong, J, Yu, S, Tao, W, Li, H, Shen, X, Ji, C, Dong, A, Ou, Y	J. Biol. Chem.	2008