Signaling by MRAS-complex mutants

Stable Identifier
Homo sapiens
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A complex of MRAS, SHOC2 and the phosphatase PP1 contributes to the activation of RAF proteins by removing an inhibitory phosphorylation that mediates binding to 14-3-3 (also known as YWHAB) proteins (Rodriguez-Viciano et al, 2006; Young et al, 2013;reviewed in Simanshu et al, 2017; Lavoie and Therrien, 2015). Activating and inactivating mutations in each of the components of this dephosphorylating complex have been identified in RASopathies as well as at low frequency in some cancers (Cordeddu et al, 2009; Hannig et al, 2014; Gripp et al, 2016; Higgin et al, 2017; Motta et al, 2016; Motta et al, 2019a,b).
Literature References
PubMed ID Title Journal Year
31059601 Clinical and functional characterization of a novel RASopathy-causing SHOC2 mutation associated with prenatal-onset hypertrophic cardiomyopathy

De Luca, A, Petrini, S, Pantaleoni, F, Mastromoro, G, D'Ambrosio, V, Pinna, V, Mazza, T, Chillemi, G, Motta, M, Versacci, P, Di Giosaffatte, N, Chandramouli, B, Ventriglia, F, Pizzuti, A, Tartaglia, M, Giancotti, A

Hum. Mutat. 2019
19684605 Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes Noonan-like syndrome with loose anagen hair

Zenker, M, Martinelli, S, Di Schiavi, E, Cordeddu, V, Ferrero, GB, Cardinale, A, Bartholdi, D, Merlo, D, Anichini, C, Iyengar, R, Tartaglia, M, Tenconi, R, Schackwitz, W, Cecchetti, S, Digilio, MC, Gelb, BD, Zampino, G, Pennacchio, LA, Bazzicalupo, P, Sarkozy, A, Ma'ayan, A, Kutsche, K, Fodale, V, Lipzen, A, Dallapiccola, B, Flex, E, Lepri, F, Martin, J, Selicorni, A, Rossi, C, Mazzanti, L

Nat. Genet. 2009
24211266 An MRAS, SHOC2, and SCRIB complex coordinates ERK pathway activation with polarity and tumorigenic growth

Young, LC, Ghatrora, R, Gewinner, C, Bender, S, Hartig, N, Burlingame, AL, Oses-Prieto, JA, Henderson, S, Vijayakumar, V, Jathoul, AP, Vietri Rudan, M, Rodriguez-Viciana, P, Lythgoe, MF, Muñoz-Alegre, M, Durdu, S

Mol. Cell 2013
25907612 Regulation of RAF protein kinases in ERK signalling

Lavoie, H, Therrien, M

Nat. Rev. Mol. Cell Biol. 2015
27264673 A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair

Aldinger, KA, Bennett, JT, Sol-Church, K, Baker, L, Timms, AE, Powell-Hamilton, N, Dobyns, WB, Gripp, KW, Tusi, J, Stabley, D

Am. J. Med. Genet. A 2016
31108500 Activating MRAS mutations cause Noonan syndrome associated with hypertrophic cardiomyopathy

Cavé, H, Altmüller, F, Lissewski, C, Zenker, M, Chahrokh-Zadeh, S, Coppola, S, Pantaleoni, F, Krumbach, OHF, Peleg, A, Hahn, A, German, A, Ahmadian, MR, Kocherscheid, L, Motta, M, Logeswaran, T, Schanze, D, Sagi-Dain, L, Munzig, A, Nakhaei-Rad, S, Tartaglia, M

Hum. Mol. Genet. 2019
28289718 Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy

Tester, DJ, Sol-Church, K, Higgins, EM, MacRae, CA, Mason-Suares, H, Ackerman, JP, Bos, JM, Urrutia, R, Gripp, KW, Ackerman, MJ

JCI Insight 2017
27466182 SHOC2 subcellular shuttling requires the KEKE motif-rich region and N-terminal leucine-rich repeat domain and impacts on ERK signalling

Cordeddu, V, Chillemi, G, Motta, M, Macioce, P, Gelb, BD, Tartaglia, M, Coppola, S, Stipo, S, Cecchetti, S, Fodale, V

Hum. Mol. Genet. 2016
25137548 A Novel SHOC2 Variant in Rasopathy

Hannig, V, Galperin, E, Phillips, JA, Jeoung, M, Jang, ER

Hum. Mutat. 2014
28666118 RAS Proteins and Their Regulators in Human Disease

McCormick, F, Nissley, DV, Simanshu, DK

Cell 2017
16630891 A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity

McCormick, F, Fried, M, Burlingame, A, Oses-Prieto, J, Rodriguez-Viciana, P

Mol. Cell 2006
Name Identifier Synonyms
esophageal carcinoma DOID:1107 carcinoma OF ESOPHAGUS, carcinoma of oesophagus, cancer of esophagus, cancer of oesophagus, carcinoma of esophagus (disorder), carcinoma of esophagus (disorder)
Noonan syndrome DOID:3490 Turner's phenotype, karyotype normal (disorder)
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