Reactome | RAF is paradoxically phosphorylated downstream of kinase-inactive RAF

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RAF is paradoxically phosphorylated downstream of kinase-inactive RAF Show undefined attributes

authored	[InstanceEdit:5693873] Rothfels, Karen, 2015-05-18
catalystActivity	[CatalystActivity:5672970] protein serine/threonine/tyrosine kinase activity of RAF activating kinases [plasma membrane]
category	transition
compartment	[Compartment:876] plasma membrane
created	[InstanceEdit:6802940] Rothfels, Karen, 2015-10-02
crossReference	[DatabaseIdentifier:12020745] Mondo:0004992
dbId	6802941
disease	[Disease:1500689] cancer
displayName	RAF is paradoxically phosphorylated downstream of kinase-inactive RAF
edited	[InstanceEdit:6802811] Rothfels, Karen, 2015-08-10
entityFunctionalStatus	[EntityFunctionalStatus:6802894] gain_of_function of mutant RAS:inactive BRAF:RAF1 [plasma membrane]
eventOf	[Pathway:R-HSA-6802955] Paradoxical activation of RAF signaling by kinase inactive BRAF - Homo sapiens
followingEvent	[Reaction:R-HSA-6802942] RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs - Homo sapiens
input	5 × [SimpleEntity:R-ALL-113592] ATP [cytosol] [Complex:R-HSA-6802674] mutant RAS:inactive BRAF:RAF1 [plasma membrane]
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:6790368] RAF inhibitors activate the MAPK pathway by relieving inhibitory autophosphorylation [LiteratureReference:6790417] Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond
maxDepth	1
modified	[InstanceEdit:9830342] Matthews, Lisa, 2023-03-08
name	RAF is paradoxically phosphorylated downstream of kinase-inactive RAF
normalReaction	[Reaction:R-HSA-5672969] Phosphorylation of RAF
output	5 × [SimpleEntity:R-ALL-29370] ADP [cytosol] [Complex:R-HSA-6802633] mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane]
precedingEvent	[Reaction:R-HSA-8936731] Inactive BRAF mutants:mutant RAS:GTP bind RAF1 - Homo sapiens
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-6802941
summation	[Summation:6802242] The enhanced dimerization of inhibited or kinase dead versio...

Referrals

(hasEvent)	[Pathway:R-HSA-6802955] Paradoxical activation of RAF signaling by kinase inactive BRAF
(precedingEvent)	[Reaction:R-HSA-6802942] RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs

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