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_7 label "Selventa" provenance.
large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
large_corpus.bel description "Approximately 61,000 statements." provenance.
large_corpus.bel version "1.4" provenance.
large_corpus.bel authoredBy _7 provenance.
assertion wasDerivedFrom large_corpus.bel provenance.
assertion wasDerivedFrom _6 provenance.
assertion hadPrimarySource 16170185 provenance.
_6 wasQuotedFrom 16170185 provenance.
_6 value "124 However, Ras-mediated recruitment of C-Raf to the cell membrane and Src activation are not the only steps involved in the activation of C-Raf. A-Raf, which is structurally similar to C-Raf, is activated in a similar manner; however, the pertinent structural and activational aspects of B-Raf differ from those of A-Raf and C-Raf. Although the structural domains and phosphorylation sites of Raf proteins differ, the greater degree of phosphorylated amino acids in B-Raf confers a 15- to 20- fold higher level of kinase activity in the basal state than either A-Raf or C-Raf, and B-Raf is therefore a much more robust activator of ERK phosphorylation.85,144,145 The differential splicing of B-raf may also account for the distinct kinase activity of the protein. In addition, the structures of several B-Raf mutants mimic the conformational changes unique to phosphorylated wild-type B-Raf, which may explain the ability of B-Raf mutants to activate ERK in the absence of stimulation. Other interactions. In addition to phosphorylation events, the activation status of C-Raf is regulated by protein-protein and protein-lipid interactions. As shown in Figure 2, C-Raf interacts with a diverse array of scaffolding proteins (kinase suppressor of Ras and MEK partner-1), adaptor proteins (Bcl-2-associated athanogene-1), chaperone proteins (Hsp90 and Hsp70), substrates (retinoblastoma protein [Rb]), lipids (phosphatidic acid, cholesterol-rich caveolae, and cytosolic lipid rafts), and cellular constituents, many of which, in turn, modulate its kinase activity.95 Activation of Downstream Effectors by Raf Activated Raf principally propagates signaling by phosphorylating the two dual-specificity MAPKKs, MEK1 and MEK2 (also referred to as MKK1 and MKK2; Figs 1 and 2). 75 The Raf isoforms are the best characterized MEK1 and MEK2 activators, and all Raf isoforms activate MEK1, whereas only B-Raf and C-Raf activate MEK2." provenance.