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RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants
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authored
[InstanceEdit:9656339] Orlic-Milacic, Marija, 2019年07月31日
catalystActivity
[CatalystActivity:9664990] guanyl-nucleotide exchange factor activity of Phosphorylated heterodimers of ERBB2 KD mutants:p-Y349,Y350-SHC1:GRB2:SOS1 [plasma membrane]
category
transition
compartment
[Compartment:70101] cytosol
[Compartment:876] plasma membrane
created
[InstanceEdit:9664992] Orlic-Milacic, Marija, 2019年10月28日
crossReference
[DatabaseIdentifier:11944892] Mondo:0004992
dbId
9664991
disease
[Disease:1500689] cancer
displayName
RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants
edited
[InstanceEdit:9665760] Orlic-Milacic, Marija, 2019年11月01日
entityFunctionalStatus
[EntityFunctionalStatus:9664989] gain_of_function of Phosphorylated heterodimers of ERBB2 KD mutants:p-Y349,Y350-SHC1:GRB2:SOS1 [plasma membrane]
eventOf
[Pathway:R-HSA-9664565] Signaling by ERBB2 KD Mutants - Homo sapiens
input
[SimpleEntity:R-ALL-29438] GTP [cytosol]
[Complex:R-HSA-109796] p21 RAS:GDP [plasma membrane]
isChimeric
false
isInDisease
true
isInferred
false
literatureReference
[LiteratureReference:9665642] HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors
[LiteratureReference:9649397] Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib
[LiteratureReference:9646776] EXEL-7647 inhibits mutant forms of ErbB2 associated with lapatinib resistance and neoplastic transformation
[LiteratureReference:9646435] Activating HER2 mutations in HER2 gene amplification negative breast cancer
[LiteratureReference:9646787] Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2)
[LiteratureReference:9646758] Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification
[LiteratureReference:9650849] Antitumor effect of afatinib, as a human epidermal growth factor receptor 2-targeted therapy, in lung cancers harboring HER2 oncogene alterations
[LiteratureReference:9647026] An Acquired
HER2
T798I
Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer
[LiteratureReference:9652195] Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2
[LiteratureReference:9664473] Mutational activation of ErbB2 reveals a new protein kinase autoinhibition mechanism
[LiteratureReference:9646962] Phosphorylation of mutationally introduced tyrosine in the activation loop of HER2 confers gain-of-function activity
[LiteratureReference:9646964] Tumor driven by gain-of-function HER2 H878Y mutant is highly sensitive to HER2 inhibitor
maxDepth
1
modified
[InstanceEdit:9830342] Matthews, Lisa, 2023年03月08日
name
RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants
normalReaction
[Reaction:R-HSA-1250463] RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-SHC1:Phosphorylated ERBB2 heterodimers
output
[SimpleEntity:R-ALL-29420] GDP [cytosol]
[Complex:R-HSA-109783] p21 RAS:GTP [plasma membrane]
precedingEvent
[Reaction:R-HSA-9664983] Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1 - Homo sapiens
releaseDate
2019年12月10日
reviewStatus
[ReviewStatus:9821382] five stars
reviewed
[InstanceEdit:9662685] Kancha, Rama Krishna, 2019年09月16日
schemaClass
Reaction
species
[Species:48887] Homo sapiens
stId
R-HSA-9664991
summation
[Summation:9664988] For the following ERBB2 KD mutants that were shown to activa...
updateTrackers
[UpdateTracker:9835686] Update Tracker - [Reaction:9664991] RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants - v85:[modifyText]
Referrals
(updatedInstance)
[UpdateTracker:9835686] Update Tracker - [Reaction:9664991] RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants - v85:[modifyText]
(hasEvent)
[Pathway:R-HSA-9664565] Signaling by ERBB2 KD Mutants
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