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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo#_8 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo#_7 http://www.w3.org/ns/prov#value Another major signaling pathway is the Ras/MAP kinase cascade [33] (fig. 1). The activated Kit recruits SH-2-containing proteins such as Grb2, Shc and SHP2. Grb2 may bind Kit either directly or indirectly through interaction with Shc or SHP2. Since Grb2 is constitutively associated with Sos, a guanine nucleotide exchange factor, the recruitment of Grb2 to the activated Kit resultes in the colocalization of Sos and Ras and the subsequent activation of Ras. This promotes the interaction of Ras with Raf serinethreonine kinase and then the activation of MEK (a MAP kinase kinase). MEK phosphorylates ERK (a MAP kinase), and ERK phosphorylates a number of substrates, including pp90rsk [33]. Imatinib mesylate also inhibits the phosphorylation of ERK [34]. This process is considered to be due to blocking of the Kit signaling by this drug. Thus, both major signaling pathways of Kit, the PI3K/Akt system and the Ras/MAP kinase cascade, are inhibited by imatinib mesylate. http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo#_7 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/15583854 http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo#_8 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/15583854 http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo#_7 http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo#pubinfo http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo http://purl.org/dc/terms/created 2014-07-03T14:30:30.086+02:00 http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAdCHdxDnTU-c8-Pfx7OsvhC6PgkwBdGKBDjNPmZVqcuo http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234