MAP2Ks phosphorylate MAPKs downstream of RAF1 mutants

Stable Identifier
R-HSA-9656214
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
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MAPK proteins are phosphorylated downstream of RAF1 mutants (Razzaque et al, 2007; Pandit et al, 2007; Kobayashi et al, 2010; Wu et al, 2012).

Literature References
PubMed ID Title Journal Year
17603482 Germline gain-of-function mutations in RAF1 cause Noonan syndrome

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

Nat. Genet. 2007
20052757 Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation

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

Hum. Mutat. 2010
22826437 Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants

Wu, X, Yin, J, Simpson, J, Kim, KH, Gu, S, Hong, JH, Bayliss, P, Backx, PH, Neel, BG, Araki, T

Mol. Cell. Biol. 2012
17603483 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy

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

Nat Genet 2007
Participants
Participates
Catalyst Activity

protein serine/threonine kinase activity of activated RAF1 mutant:scaffold:p-2S MAP2K:MAPK complex [plasma membrane]

Normal reaction
Functional status

Gain of function of activated RAF1 mutant:scaffold:p-2S MAP2K:MAPK complex [plasma membrane]

Status
Disease
Name Identifier Synonyms
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
Costello syndrome DOID:0050469 Faciocutaneoskeletal Syndrome, FCS SYNDROME
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Noonan syndrome DOID:3490 Turner's phenotype, karyotype normal (disorder)
hypertrophic cardiomyopathy DOID:11984 familial hypertrophic cardiomyopathy, hypertrophic obstructive cardiomyopathy
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