KRAS4B is phosphorylated on serine 181

Stable Identifier
R-HSA-9653503
Type
Reaction [transition]
Species
Homo sapiens
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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
24033119 Marine natural products: bryostatins in preclinical and clinical studies

Kollár, P, Rajchard, J, Balounová, Z, Pazourek, J

Pharm Biol 2014
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
23943869 Oncogenic K-ras segregates at spatially distinct plasma membrane signaling platforms according to its phosphorylation status

Barceló, C, Paco, N, Beckett, AJ, Alvarez-Moya, B, Garrido, E, Gelabert, M, Tebar, F, Jaumot, M, Prior, I, Agell, N

J. Cell. Sci. 2013
9436858 Establishment of a human pancreatic tumor xenograft model: potential application for preclinical evaluation of novel therapeutic agents

Mohammad, RM, Dugan, MC, Mohamed, AN, Almatchy, VP, Flake, TM, Dergham, ST, Shields, AF, Al-Katib, AA, Vaitkevicius, VK, Sarkar, FH

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, Casteel, DE, Prakash, P, Tan, L, van der Hoeven, D, Salim, AA, Kim, C, Capon, RJ, Lacey, E, Cunha, SR, Gorfe, AA, Hancock, JF

Mol. Cell. Biol. 2016
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
16483930 PKC regulates a farnesyl-electrostatic switch on K-Ras that promotes its association with Bcl-XL on mitochondria and induces apoptosis

Bivona, TG, Quatela, SE, Bodemann, BO, Ahearn, IM, Soskis, MJ, Mor, A, Miura, J, Wiener, HH, Wright, L, Saba, SG, Yim, D, Fein, A, Pérez De Castro, I, Li, C, Thompson, CB, Cox, AD, Philips, MR

Mol. Cell 2006
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
25713064 Mechanisms of membrane binding of small GTPase K-Ras4B farnesylated hypervariable region

Jang, H, Abraham, SJ, Chavan, TS, Hitchinson, B, Khavrutskii, L, Tarasova, NI, Nussinov, R, Gaponenko, V

J. Biol. Chem. 2015
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Title
protein serine/threonine kinase activity of PKCZ,PRKG2 [plasma membrane]
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