S-Farn-Me KRAS4B binds calmodulin

Stable Identifier
R-HSA-9653585
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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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
18182391 Identification of essential interacting elements in K-Ras/calmodulin binding and its role in K-Ras localization

Lopez-Alcalá, C, Alvarez-Moya, B, Villalonga, P, Calvo, M, Bachs, O, Agell, N

J. Biol. Chem. 2008
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
16043511 Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca2+/calmodulin

Fivaz, M, Meyer, T

J. Cell Biol. 2005
11585916 Calmodulin binds to K-Ras, but not to H- or N-Ras, and modulates its downstream signaling

Villalonga, P, López-Alcalá, C, Bosch, M, Chiloeches, A, Rocamora, N, Gil, J, Marais, R, Marshall, CJ, Bachs, O, Agell, N

Mol. Cell. Biol. 2001
29311131 Posttranslational Modifications of RAS Proteins

Ahearn, I, Zhou, M, Philips, MR

Cold Spring Harb Perspect Med 2018
26085527 The Key Role of Calmodulin in KRAS-Driven Adenocarcinomas

Nussinov, R, Muratcioglu, S, Tsai, CJ, Jang, H, Gursoy, A, Keskin, O

Mol. Cancer Res. 2015
20802526 K-Ras4B phosphorylation at Ser181 is inhibited by calmodulin and modulates K-Ras activity and function

Alvarez-Moya, B, López-Alcalá, C, Drosten, M, Bachs, O, Agell, N

Oncogene 2010
12727204 Ca2+/calmodulin binds and dissociates K-RasB from membrane

Sidhu, RS, Clough, RR, Bhullar, RP

Biochem. Biophys. Res. Commun. 2003
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