Reactome | KRAS4B is phosphorylated on serine 181

KRAS4B is phosphorylated on serine 181

Stable Identifier

R-HSA-9653503

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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KRAS4B is phosphorylated on serine 181 by PKC theta or cGMP dependent protein kinase 2 (PRKG2) (Bivona et al, 2006; Alvarez-Moya et al, 2010; Cho et al, 2016; reviewed in Ahearn et al, 2018). Serine 181 lies in a polybasic region unique to KRAS upstream of the CaaX motif. Phosphorylation at this position decreases the affinity of KRAS4B for the membrane and promotes internalization (Bivona et al, 2006; Barcelo et al, 2013; Jang et al, 2015). S181 phosphorylation has been shown to restrict cellular proliferation and oncogenesis in part by promoting BCL2L (also known as BCL-XL)-dependent apoptosis (Bivona et al, 2006; Mohammad et al, 1998; Kollar et al, 2014). Phosphorylation at S181 may also interfere with the binding of calmodulin to KRAS4B, thus disrupting calmodulin-dependent supression of signaling downstream of RAS (Wang et al, 2001; Villalonga et al, 2001).

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
24033119	Marine natural products: bryostatins in preclinical and clinical studies Pazourek, J, Kollár, P, Rajchard, J, Balounová, Z	Pharm Biol	2014
23943869	Oncogenic K-ras segregates at spatially distinct plasma membrane signaling platforms according to its phosphorylation status Tebar, F, Beckett, AJ, Agell, N, Barceló, C, Prior, I, Paco, N, Jaumot, M, Alvarez-Moya, B, Garrido, E, Gelabert, M	J. Cell. Sci.	2013
9436858	Establishment of a human pancreatic tumor xenograft model: potential application for preclinical evaluation of novel therapeutic agents Vaitkevicius, VK, Sarkar, FH, Dergham, ST, Almatchy, VP, Flake, TM, Al-Katib, AA, Shields, AF, Mohammad, RM, Dugan, MC, Mohamed, AN	Pancreas	1998
27697864	AMPK and Endothelial Nitric Oxide Synthase Signaling Regulates K-Ras Plasma Membrane Interactions via Cyclic GMP-Dependent Protein Kinase 2 Cho, KJ, Capon, RJ, Casteel, DE, Hancock, JF, Lacey, E, Cunha, SR, Salim, AA, Prakash, P, Tan, L, Gorfe, AA, Kim, C, van der Hoeven, D	Mol. Cell. Biol.	2016
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
16483930	PKC regulates a farnesyl-electrostatic switch on K-Ras that promotes its association with Bcl-XL on mitochondria and induces apoptosis Philips, MR, Bivona, TG, Thompson, CB, Ahearn, IM, Mor, A, Pérez De Castro, I, Saba, SG, Yim, D, Cox, AD, Bodemann, BO, Wiener, HH, Soskis, MJ, Fein, A, Miura, J, Quatela, SE, Li, C, Wright, L	Mol. Cell	2006
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
25713064	Mechanisms of membrane binding of small GTPase K-Ras4B farnesylated hypervariable region Nussinov, R, Tarasova, NI, Khavrutskii, L, Jang, H, Abraham, SJ, Gaponenko, V, Hitchinson, B, Chavan, TS	J. Biol. Chem.	2015