Reactome | RAF/MAP kinase cascade

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RAF/MAP kinase cascade Show undefined attributes

authored	[InstanceEdit:5674528] Rothfels, Karen, 2015-02-12
created	[InstanceEdit:5673002] Rothfels, Karen, 2015-02-06
crossReference	[DatabaseIdentifier:12819433] BioModels Database:BIOMD0000000653 [DatabaseIdentifier:12819435] BioModels Database:BIOMD0000000656 [DatabaseIdentifier:12819477] BioModels Database:BIOMD0000000651 [DatabaseIdentifier:12819437] BioModels Database:BIOMD0000000648 [DatabaseIdentifier:12819471] BioModels Database:BIOMD0000000175 [DatabaseIdentifier:12819441] BioModels Database:BIOMD0000000655 [DatabaseIdentifier:12819443] BioModels Database:BIOMD0000000652 [DatabaseIdentifier:12819431] BioModels Database:BIOMD0000000883 [DatabaseIdentifier:12819481] BioModels Database:BIOMD0000000399 [DatabaseIdentifier:12819483] BioModels Database:BIOMD0000000019 [DatabaseIdentifier:12819485] BioModels Database:BIOMD0000000424 [DatabaseIdentifier:12819445] BioModels Database:BIOMD0000000654
dbId	5673001
deleted	[Deleted:6798808] Deletion of instance: 109869 [Deleted:9028794] Deletion of instance: 197529 [Deleted:9608142] Deletion of instance: 197529
diseasePathways	[Pathway:R-HSA-9753510] Signaling by RAS GAP mutants - Homo sapiens [Pathway:R-HSA-9753512] Signaling by RAS GTPase mutants - Homo sapiens [Pathway:R-HSA-9649913] RAS GTPase cycle mutants - Homo sapiens [Pathway:R-HSA-9649948] Signaling downstream of RAS mutants - Homo sapiens [Pathway:R-HSA-6802949] Signaling by RAS mutants - Homo sapiens [Pathway:R-HSA-9652817] Signaling by MAPK mutants - Homo sapiens [Pathway:R-HSA-6802948] Signaling by high-kinase activity BRAF mutants - Homo sapiens [Pathway:R-HSA-6802946] Signaling by moderate kinase activity BRAF mutants - Homo sapiens [Pathway:R-HSA-9652169] Signaling by MAP2K mutants - Homo sapiens [Pathway:R-HSA-9726840] SHOC2 M1731 mutant abolishes MRAS complex function - Homo sapiens [Pathway:R-HSA-9726842] Gain-of-function MRAS complexes activate RAF signaling - Homo sapiens [Pathway:R-HSA-9660537] Signaling by MRAS-complex mutants - Homo sapiens [Pathway:R-HSA-6802955] Paradoxical activation of RAF signaling by kinase inactive BRAF - Homo sapiens [Pathway:R-HSA-9656223] Signaling by RAF1 mutants - Homo sapiens [Pathway:R-HSA-6802953] RAS signaling downstream of NF1 loss-of-function variants - Homo sapiens [Pathway:R-HSA-6802952] Signaling by BRAF and RAF1 fusions - Homo sapiens [Pathway:R-HSA-6802957] Oncogenic MAPK signaling - Homo sapiens
displayName	RAF/MAP kinase cascade
doi	10.3180/R-HSA-5673001.9
edited	[InstanceEdit:5674528] Rothfels, Karen, 2015-02-12
eventOf	[Pathway:R-HSA-5684996] MAPK1/MAPK3 signaling - Homo sapiens
figure	[Figure:1996283] /figures/Pathway_Illustrations/RASMAPK_72_oicr.png
goBiologicalProcess	[GO_BiologicalProcess:21714] MAPK cascade
hasDiagram	true
hasEHLD	false
hasEvent	[Pathway:R-HSA-9648002] RAS processing - Homo sapiens [Reaction:R-HSA-9649736] RAS intrinsic GTPase activity hydrolyzes GTP to GDP - Homo sapiens [Reaction:R-HSA-9649735] Intrinsic nucleotide exchange on RAS - Homo sapiens [Reaction:R-HSA-5672965] RAS GEFs promote RAS nucleotide exchange - Homo sapiens [Reaction:R-HSA-9658253] RAS:GTP binds PI3K - Homo sapiens [Reaction:R-HSA-9660557] RAS:GTP binds RAL GDS proteins - Homo sapiens [Pathway:R-HSA-5673000] RAF activation - Homo sapiens [Pathway:R-HSA-5674135] MAP2K and MAPK activation - Homo sapiens [Reaction:R-HSA-5674385] p-T,Y MAPKs dimerize - Homo sapiens [BlackBoxEvent:R-HSA-5674387] Phosphorylated MAPKs translocate into the nucleus - Homo sapiens [Reaction:R-HSA-5675206] PEA15 binds MAPK monomers and dimers - Homo sapiens [Pathway:R-HSA-5675221] Negative regulation of MAPK pathway - Homo sapiens [Pathway:R-HSA-5658442] Regulation of RAS by GAPs - Homo sapiens
isInDisease	false
isInferred	false
lastUpdatedDate	2023-06-07
literatureReference	[LiteratureReference:5672144] "RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway [LiteratureReference:5672517] RAF protein-serine/threonine kinases: structure and regulation [LiteratureReference:208231] Integrating signals from RTKs to ERK/MAPK [LiteratureReference:1497944] The RAF proteins take centre stage [LiteratureReference:5673943] ERK1/2 MAP kinases: structure, function, and regulation [LiteratureReference:5673960] MEK1/2 dual-specificity protein kinases: structure and regulation [LiteratureReference:5683024] Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update [LiteratureReference:5683022] MAP kinases and the control of nuclear events [LiteratureReference:5683028] The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation [LiteratureReference:5672150] Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases [LiteratureReference:5673962] Protein scaffolds in MAP kinase signalling [LiteratureReference:5672236] Mutations of the BRAF gene in human cancer [LiteratureReference:5683027] Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer [LiteratureReference:5683020] BRAFV600E: implications for carcinogenesis and molecular therapy
maxDepth	4
modified	[InstanceEdit:11108703] Weiser, Joel, 2026-03-16
name	RAF/MAP kinase cascade
orthologousEvent	[Pathway:R-RNO-5673001] RAF/MAP kinase cascade - Rattus norvegicus [Pathway:R-MMU-5673001] RAF/MAP kinase cascade - Mus musculus [Pathway:R-CFA-5673001] RAF/MAP kinase cascade - Canis familiaris [Pathway:R-BTA-5673001] RAF/MAP kinase cascade - Bos taurus [Pathway:R-SSC-5673001] RAF/MAP kinase cascade - Sus scrofa [Pathway:R-DRE-5673001] RAF/MAP kinase cascade - Danio rerio [Pathway:R-CEL-5673001] RAF/MAP kinase cascade - Caenorhabditis elegans [Pathway:R-XTR-5673001] RAF/MAP kinase cascade - Xenopus tropicalis [Pathway:R-GGA-5673001] RAF/MAP kinase cascade - Gallus gallus [Pathway:R-DME-5673001] RAF/MAP kinase cascade - Drosophila melanogaster [Pathway:R-DDI-5673001] RAF/MAP kinase cascade - Dictyostelium discoideum [Pathway:R-SCE-5673001] RAF/MAP kinase cascade - Saccharomyces cerevisiae [Pathway:R-PFA-5673001] RAF/MAP kinase cascade - Plasmodium falciparum [Pathway:R-SPO-5673001] RAF/MAP kinase cascade - Schizosaccharomyces pombe
precedingEvent	[Reaction:R-HSA-9607304] SOS1-mediated nucleotide exchange of RAS downstream of FLT3 - Homo sapiens [BlackBoxEvent:R-HSA-9606784] Active FLT3:GRB2:p-Y-GAB2 binds PTPN11 - Homo sapiens [Reaction:R-HSA-9604969] Active FLT3 binds PTPN11 - Homo sapiens
releaseDate	2015-06-17
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:5690572] Roskoski, Robert Jr, 2015-04-28
schemaClass	Pathway
species	[Species:48887] Homo sapiens
stId	R-HSA-5673001
summation	[Summation:5683030] The RAS-RAF-MEK-ERK pathway regulates processes such as prol...
updateTrackers	[UpdateTracker:9782910] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v58:[updateIndirectRLE] [UpdateTracker:9783648] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v56:[modifyText] [UpdateTracker:9776933] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v73:[addHasEvent, updateContainedPathway] [UpdateTracker:9778933] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v67:[updateIndirectRLE] [UpdateTracker:9783801] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v55:[updateIndirectRLE] [UpdateTracker:9777599] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v70:[updateIndirectRLE] [UpdateTracker:9835696] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v85:[updateIndirectRLE] [UpdateTracker:9780602] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v62:[updateIndirectRLE] [UpdateTracker:9775877] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v78:[updateIndirectRLE]

Referrals

(hasEvent)	[Pathway:R-HSA-5684996] MAPK1/MAPK3 signaling
(hasEncapsulatedEvent)	[Pathway:R-HSA-2586552] Signaling by Leptin [Pathway:R-HSA-201556] Signaling by ALK [Pathway:R-HSA-9842663] Signaling by LTK [Pathway:R-HSA-9607240] FLT3 Signaling [Pathway:R-HSA-8853659] RET signaling [Pathway:R-HSA-1257604] PIP3 activates AKT signaling [Pathway:R-HSA-9648002] RAS processing [Pathway:R-HSA-1227986] Signaling by ERBB2 [Pathway:R-HSA-8848021] Signaling by PTK6 [Pathway:R-HSA-187037] Signaling by NTRK1 (TRKA) [Pathway:R-HSA-6806834] Signaling by MET [Pathway:R-HSA-1236394] Signaling by ERBB4 [Pathway:R-HSA-8878166] Transcriptional regulation by RUNX2 [Pathway:R-HSA-1433557] Signaling by SCF-KIT [Pathway:R-HSA-186797] Signaling by PDGF [Pathway:R-HSA-512988] Interleukin-3, Interleukin-5 and GM-CSF signaling [Pathway:R-HSA-451927] Interleukin-2 family signaling [Pathway:R-HSA-5654738] Signaling by FGFR2 [Pathway:R-HSA-5654741] Signaling by FGFR3 [Pathway:R-HSA-5654736] Signaling by FGFR1 [Pathway:R-HSA-5654743] Signaling by FGFR4 [Pathway:R-HSA-375165] NCAM signaling for neurite out-growth [Pathway:R-HSA-881907] Gastrin-CREB signalling pathway via PKC and MAPK [Pathway:R-HSA-74752] Signaling by Insulin receptor [Pathway:R-HSA-442755] Activation of NMDA receptors and postsynaptic events [Pathway:R-HSA-9034015] Signaling by NTRK3 (TRKC) [Pathway:R-HSA-9006115] Signaling by NTRK2 (TRKB) [Pathway:R-HSA-2404192] Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) [Pathway:R-HSA-2454202] Fc epsilon receptor (FCERI) signaling [Pathway:R-HSA-2172127] DAP12 interactions [Pathway:R-HSA-194138] Signaling by VEGF [Pathway:R-HSA-177929] Signaling by EGFR [Pathway:R-HSA-9009391] Extra-nuclear estrogen signaling
(normalPathway)	[Pathway:R-HSA-9753510] Signaling by RAS GAP mutants [Pathway:R-HSA-9753512] Signaling by RAS GTPase mutants [Pathway:R-HSA-9649913] RAS GTPase cycle mutants [Pathway:R-HSA-9649948] Signaling downstream of RAS mutants [Pathway:R-HSA-6802949] Signaling by RAS mutants [Pathway:R-HSA-9652817] Signaling by MAPK mutants [Pathway:R-HSA-6802948] Signaling by high-kinase activity BRAF mutants [Pathway:R-HSA-6802946] Signaling by moderate kinase activity BRAF mutants [Pathway:R-HSA-9652169] Signaling by MAP2K mutants [Pathway:R-HSA-9726840] SHOC2 M1731 mutant abolishes MRAS complex function [Pathway:R-HSA-9726842] Gain-of-function MRAS complexes activate RAF signaling [Pathway:R-HSA-9660537] Signaling by MRAS-complex mutants [Pathway:R-HSA-6802955] Paradoxical activation of RAF signaling by kinase inactive BRAF [Pathway:R-HSA-9656223] Signaling by RAF1 mutants [Pathway:R-HSA-6802953] RAS signaling downstream of NF1 loss-of-function variants [Pathway:R-HSA-6802952] Signaling by BRAF and RAF1 fusions [Pathway:R-HSA-6802957] Oncogenic MAPK signaling
(replacementInstances)	[Deleted:6798808] Deletion of instance: 109869 [Deleted:9028794] Deletion of instance: 197529 [Deleted:9608142] Deletion of instance: 197529
(updatedInstance)	[UpdateTracker:9782910] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v58:[updateIndirectRLE] [UpdateTracker:9783648] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v56:[modifyText] [UpdateTracker:9776933] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v73:[addHasEvent, updateContainedPathway] [UpdateTracker:9778933] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v67:[updateIndirectRLE] [UpdateTracker:9783801] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v55:[updateIndirectRLE] [UpdateTracker:9777599] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v70:[updateIndirectRLE] [UpdateTracker:9835696] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v85:[updateIndirectRLE] [UpdateTracker:9780602] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v62:[updateIndirectRLE] [UpdateTracker:9775877] Update Tracker - [Pathway:5673001] RAF/MAP kinase cascade - v78:[updateIndirectRLE]

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