Reactome | S-Farn-Me KRAS4B binds calmodulin

S-Farn-Me KRAS4B binds calmodulin

Stable Identifier

R-HSA-9653585

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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KRAS4B, unique among RAS isoforms, has been shown to bind to calmodulin (Villalonga et al, 2001; Lopez-Alcala et al, 2008). This interaction is thought to decrease the affinity of KRAS4B for the plasma membrane (Fivaz and Meyer, 2005; Sidhu et al, 2003; reviewed in Ahearn et al, 2018; Nussinov et al, 2015). Interaction between oncogenic KRAS4B and calmodulin has been shown to promote tumorigenesis by interfering with the activation of CAMK2. This in turn relieves the suppression of beta-catenin dependent signaling mediated by the non-canonical WNT signaling pathway (Wang et al, 2015).
The interaction between KRAS4B and calmodulin is inhibited by PKC- or PRKG2-dependent KRAS4B phosphorylation at serine 181 (Wang et al, 2015; Alvarez-Moya et al, 2010; reviewed in Ahearn et al, 2018).

Literature References

PubMed ID	Title	Journal	Year
26590425	K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling Balmain, A, Galeas, J, Wang, MT, To, MD, McCormick, F, Delrosario, R, Holderfield, M	Cell	2015
18182391	Identification of essential interacting elements in K-Ras/calmodulin binding and its role in K-Ras localization Lopez-Alcalá, C, Villalonga, P, Alvarez-Moya, B, Agell, N, Calvo, M, Bachs, O	J. Biol. Chem.	2008
16043511	Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca2+/calmodulin Meyer, T, Fivaz, M	J. Cell Biol.	2005
11585916	Calmodulin binds to K-Ras, but not to H- or N-Ras, and modulates its downstream signaling Villalonga, P, Rocamora, N, Bosch, M, Agell, N, Gil, J, López-Alcalá, C, Marshall, CJ, Chiloeches, A, Bachs, O, Marais, R	Mol. Cell. Biol.	2001
29311131	Posttranslational Modifications of RAS Proteins Philips, MR, Zhou, M, Ahearn, I	Cold Spring Harb Perspect Med	2018
26085527	The Key Role of Calmodulin in KRAS-Driven Adenocarcinomas Nussinov, R, Jang, H, Keskin, O, Tsai, CJ, Muratcioglu, S, Gursoy, A	Mol. Cancer Res.	2015
20802526	K-Ras4B phosphorylation at Ser181 is inhibited by calmodulin and modulates K-Ras activity and function Agell, N, López-Alcalá, C, Drosten, M, Bachs, O, Alvarez-Moya, B	Oncogene	2010
12727204	Ca2+/calmodulin binds and dissociates K-RasB from membrane Bhullar, RP, Clough, RR, Sidhu, RS	Biochem. Biophys. Res. Commun.	2003