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http://resource.belframework.org/belframework/1.0/knowledge/small_corpus.bel http://purl.org/dc/elements/1.1/description Approximately 2000 hand curated statements drawn from 57 PubMeds. http://resource.belframework.org/belframework/1.0/knowledge/small_corpus.bel http://purl.org/dc/elements/1.1/rights Copyright (c) 2011-2012, Selventa. All Rights Reserved. http://resource.belframework.org/belframework/1.0/knowledge/small_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Small Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/small_corpus.bel http://purl.org/dc/terms/license Creative Commons Attribution-Non-Commercial-ShareAlike 3.0 Unported License http://resource.belframework.org/belframework/1.0/knowledge/small_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAbowMwHGB11JdP_33IzgpxlpcEqqM_v-ib3BEBkGqCQ8#_8 http://resource.belframework.org/belframework/1.0/knowledge/small_corpus.bel http://purl.org/pav/version 1.6 http://www.tkuhn.ch/bel2nanopub/RAbowMwHGB11JdP_33IzgpxlpcEqqM_v-ib3BEBkGqCQ8#_7 http://www.w3.org/ns/prov#value Phosphorylation. Raf is principally activated by phosphorylation of specific amino acid residues as shown for each isoform in Figure 4. From an evolutionary standpoint, the Raf activation sites are highly conserved from yeast to humans. Several amino acids in Raf, particularly serine (S) 259 and S621, which bind 14-3-3 and maintain C-Raf in a closed auto-inhibited conformation, are phosphorylated in the basal state.137 On stimulation, Ras-GTP displaces 14-3-3 from S259, and C-Raf is translocated to the cell membrane, where it can be dephosphorylated at S259 by protein phosphatase 2A or other phosphatases.126 S259 also represents the site of inhibitory phosphorylation by PKB/Akt, PKA, and serum glucocorticoid-inducible kinase.121,138,139 Phosphorylation at S621 seems to have greater significance because mutations at this site inactivate Raf's kinase activity. 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