Reactome | Active calmodulin binds CAMK2

Active calmodulin binds CAMK2

Stable Identifier

R-HSA-4332359

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Calcium release in response to WNT5A has been shown to activate calcium/calmodulin-dependent protein kinase 2 (CAMK2) (Kuhl et al, 2000; Ishitani et al, 2003a). Human cells have 4 genes encoding CAMK: alpha, beta, delta and gamma. Alpha and beta isoforms are expressed in neuronal tissue while delta and gamma isoforms have broad tissue distribution. The enzyme exists as either a homo- or hetero- dodecamer of ill-defined stoichiometry. In the inactive state, the autoinhibitory loop of CAMK2 blocks the active site. Upon binding of Ca2+/calmodulin, the autoinhibitory loop is displaced, allowing subsequent autophosphorylation at T286 in CAMK2 alpha and activation of the kinase (reviewed in Stratton et al, 2013). WNT-dependent activation of CAMK2 is inhibited by an interaction between oncogenic KRAS4B and calmodulin. This promotes tumorigenesis by relieving the suppression of beta-catenin dependent signaling mediated by the non-canonical WNT signaling pathway (Wang et al, 2015).

Literature References

PubMed ID	Title	Journal	Year
26590425	K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling Wang, MT, Holderfield, M, Galeas, J, Delrosario, R, To, MD, Balmain, A, McCormick, F	Cell	2015
12482967	The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling Ishitani, T, Kishida, S, Hyodo-Miura, J, Ueno, N, Yasuda, J, Waterman, M, Shibuya, H, Moon, RT, Ninomiya-Tsuji, J, Matsumoto, K	Mol. Cell. Biol.	2003
10777564	Ca(2+)/calmodulin-dependent protein kinase II is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus Kühl, M, Sheldahl, LC, Malbon, CC, Moon, RT	J. Biol. Chem.	2000
23632248	Structural studies on the regulation of Ca2+/calmodulin dependent protein kinase II Stratton, MM, Chao, LH, Schulman, H, Kuriyan, J	Curr. Opin. Struct. Biol.	2013