Reactome | RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs

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RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs Show undefined attributes

authored	[InstanceEdit:5693873] Rothfels, Karen, 2015-05-18
category	binding
compartment	[Compartment:876] plasma membrane
created	[InstanceEdit:6802944] Rothfels, Karen, 2015-10-02
dbId	6802942
disease	[Disease:1500689] cancer
displayName	RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs
edited	[InstanceEdit:6802811] Rothfels, Karen, 2015-08-10
entityFunctionalStatus	[EntityFunctionalStatus:6802897] gain_of_function of mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane]
eventOf	[Pathway:R-HSA-6802955] Paradoxical activation of RAF signaling by kinase inactive BRAF - Homo sapiens
followingEvent	[Reaction:R-HSA-6802943] RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks - Homo sapiens
input	[DefinedSet:R-HSA-5672716] MAP2K homo/heterodimers [cytosol] [DefinedSet:R-HSA-169291] MAPKs [cytosol] [Complex:R-HSA-6802633] mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane] [CandidateSet:R-HSA-5672717] RAF/MAPK scaffolds [cytosol]
isChimeric	false
isInDisease	true
isInferred	false
literatureReference	[LiteratureReference:5672469] Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF [LiteratureReference:5672291] Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization [LiteratureReference:5672195] Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF [LiteratureReference:6790390] RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF [LiteratureReference:6790370] RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth [LiteratureReference:6790420] Targeting RAS-ERK signalling in cancer: promises and challenges [LiteratureReference:6799065] Regulation of RAF protein kinases in ERK signalling [LiteratureReference:5672246] Raf family kinases: old dogs have learned new tricks
modified	[InstanceEdit:9830342] Matthews, Lisa, 2023-03-08
name	RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs
normalReaction	[Reaction:R-HSA-5672972] MAP2Ks and MAPKs bind to the activated RAF complex
output	[Complex:R-HSA-6802636] RAS:GTP:inactive p-RAF:MAP2Ks:MAPKs:scaffold proteins [plasma membrane]
precedingEvent	[Reaction:R-HSA-6802941] RAF is paradoxically phosphorylated downstream of kinase-inactive RAF - Homo sapiens
regulatedBy	[NegativeRegulation:R-HSA-8936736] Negative regulation by 'p21 RAS:GTP:activated RAF1 homo/heterodimer:PEBP1 [plasma membrane]'
releaseDate	2016-09-19
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:8933498] Stephens, Robert M, 2016-08-05
schemaClass	Reaction
species	[Species:48887] Homo sapiens
stId	R-HSA-6802942
summation	[Summation:6802190] Dimerization of kinase-dead or inhibited versions of BRAF to...

Referrals

(hasEvent)	[Pathway:R-HSA-6802955] Paradoxical activation of RAF signaling by kinase inactive BRAF
(precedingEvent)	[Reaction:R-HSA-6802943] RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks