CR2 RAF1 mutants don't bind YWHAB

Stable Identifier
Reaction [transition]
Homo sapiens
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RAF1 mutants have been identified in both RASopathies and various cancers that show elevated levels of signaling through MAP2K and MAPK (Kobayashi et al, 2010; Razzaque et al, 2007; Krauthammer et al, 2015; Pandit et al, 2007; Lee et al, 2011). RAF1 proteins with mutations that cluster in the conserved region 2 (CR2) domain of RAF1 show decreased levels of phosphorylation on S259, which is required for the interaction of RAF1 with the YWHAB 14-3-3 proteins (Kobayashi et al, 2010). Consistent with this CR2 RAF1 mutants show decreased interaction with YWHAB and increased downstream signaling (Kobayashi et al, 2010; Pandit et al, 2007; Lee et al, 2011).
Literature References
PubMed ID Title Journal Year
26214590 Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun-exposed melanomas

Narayan, D, Straub, R, McCusker, JP, Kluger, HM, Ariyan, S, Pornputtapong, N, Ma, S, Schlessinger, J, Sznol, M, Krauthammer, M, Serin, M, Mane, S, Bosenberg, M, Wu, C, Halaban, R, Lifton, RP, Evans, P, Bacchiocchi, A, Kong, Y, Cheng, E

Nat. Genet. 2015
20052757 Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation

David, A, Aoki, Y, Kure, S, Matsubara, Y, Lapunzina, P, Gillessen-Kaesbach, G, Ohata, T, Verloes, A, Cavé, H, Kurosawa, K, Ando, T, Nakagawa, N, Narumi, Y, Ohashi, H, Takada, F, Philip, N, Mizuno, S, Tsuchiya, S, Sakazume, S, Niihori, T, Wieczorek, D, Fujiwara, I, Okamoto, N, Kawame, H, Kobayashi, T, Meneses, AG, Guliyeva, A

Hum. Mutat. 2010
17603482 Germline gain-of-function mutations in RAF1 cause Noonan syndrome

Kamisago, M, Nakagawa, M, Hirota, H, Muneuchi, J, Matsushima, M, Mizuno, K, Momma, K, Higashinakagawa, T, Komoike, Y, Fujiwara, Y, Amo, R, Furutani, M, Razzaque, MA, Nishizawa, T, Yagi, H, Katayama, H, Tokuyama, M, Matsuoka, R

Nat. Genet. 2007
17603483 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy

Ackerman, MJ, Marino, B, Zampino, G, Pennacchio, LA, Bos, JM, Martinelli, S, Gelb, BD, Mazzanti, L, Lepri, F, Faul, C, Rossi, C, López Siguero, JP, Esposito, G, Carta, C, Selicorni, A, Tenconi, R, Oishi, K, Pogna, EA, Torrente, I, Pandit, B, Dallapiccola, B, Mundel, P, Ustaszewska, A, Schackwitz, W, Sarkozy, A, Digilio, MC, Landstrom, A, Ommen, SR, Tartaglia, M

Nat Genet 2007
21784453 Spectrum of mutations in Noonan syndrome and their correlation with phenotypes

Yoo, HW, Lee, BH, Kim, GH, Kim, JM, Jin, HY, Choi, JH

J. Pediatr. 2011
Normal reaction
Functional status

Loss of function of p-S621 RAF1 CR2 mutants [cytosol]

Name Identifier Synonyms
Costello syndrome DOID:0050469 Faciocutaneoskeletal Syndrome, FCS SYNDROME
LEOPARD syndrome DOID:14291 Generalized lentiginosis, Multiple lentigines syndrome, Moynahan syndrome, Cardiocutaneous syndrome, Capute-Rimoin-Konigsmark-Esterly-Richardson syndrome, Lentiginosis profusa syndrome, Gorlin syndrome II, Progressive cardiomyopathic lentiginosis
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Noonan syndrome DOID:3490 Turner's phenotype, karyotype normal (disorder)
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