Reactome | Ca2+ activates Calpain2 (m-Calpain)

Ca2+ activates Calpain2 (m-Calpain)

Stable Identifier

R-HSA-9861511

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

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Cellular responses to stimuli (Homo sapiens)

- Cellular responses to mechanical stimuli (Homo sapiens)
  - Response of endothelial cells to shear stress (Homo sapiens)
    - High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells (Homo sapiens)
      - Ca2+ activates Calpain2 (m-Calpain) (Homo sapiens)
    - Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells (Homo sapiens)
      - Ca2+ activates Calpain2 (m-Calpain) (Homo sapiens)

General

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Calpain2 (m-Calpain, CAPN2:CAPNS) is a heterodimeric protease complex containing a large, catalytic subunit (CAPN2) and a small subunit (CAPNS) (Schád et al. 2002). Calpain2 is activated by millimolar concentrations of calcium ions in vitro and micromolar concentrations in vivo (reviewed in Zhang et al. 2017). Calpain2 binds several calcium ions (Hata et al. 2001, Hanna et al. 2008, inferred from the porcine homolog in Lin et al. 1997) and calcium bound to a negatively charged loop of CAPN2 is believed to cause a change in conformation that brings the subdomains of the catalytic center together (Strobl et al. 2000, Hata et al. 2001, Reverter et al. 2001, inferred from the rat homolog in Hosfield et al. 1999). The protease activity of Calpain2 is activated in endothelial cells during laminar flow shear stress (Miyazaki et al. 2007) and during turbulent flow shear stress (Miyazaki et al. 2010).

Literature References

PubMed ID	Title	Journal	Year
19020623	Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin Campbell, RL, Davies, PL, Hanna, RA	Nature	2008
11853546	A novel human small subunit of calpains Friedrich, P, Schád, E, Jékely, G, Farkas, A, Tompa, P	Biochem. J.	2002
10639123	The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium Strobl, S, Braun, M, Nakagawa, K, Masumoto, H, Bode, W, Suzuki, K, Irie, A, Huber, R, Bourenkow, G, Bartunik, H, Fernandez-Catalan, C, Sorimachi, H	Proc. Natl. Acad. Sci. U.S.A.	2000
11470267	Domain II of m-calpain is a Ca(2+)-dependent cysteine protease Nakagawa, K, Hata, S, Abe, K, Suzuki, K, Maeda, T, Sorimachi, H	FEBS Lett	2001