Reactome | Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1

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Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1 Show undefined attributes

authored	[InstanceEdit:9656339] Orlic-Milacic, Marija, 2019-07-31
category	binding
compartment	[Compartment:876] plasma membrane
created	[InstanceEdit:9664982] Orlic-Milacic, Marija, 2019-10-28
crossReference	[DatabaseIdentifier:12020745] Mondo:0004992
dbId	9664983
disease	[Disease:1500689] cancer
displayName	Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1
edited	[InstanceEdit:9665760] Orlic-Milacic, Marija, 2019-11-01
entityFunctionalStatus	[EntityFunctionalStatus:9664980] gain_of_function of Phosphorylated heterodimers of ERBB2 KD mutants:p-Y349,Y350-SHC1 [plasma membrane]
eventOf	[Pathway:R-HSA-9664565] Signaling by ERBB2 KD Mutants - Homo sapiens
followingEvent	[Reaction:R-HSA-9664991] RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants - Homo sapiens
input	[Complex:R-HSA-109797] GRB2-1:SOS1 [cytosol] [Complex:R-HSA-9664975] Phosphorylated heterodimers of ERBB2 KD mutants:p-Y349,Y350-SHC1 [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, 2023-03-08
name	Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1
normalReaction	[Reaction:R-HSA-1250486] Recruitment of GRB2:SOS1 to p-SHC1 in complex with phosphorylated ERBB2 heterodimers
output	[Complex:R-HSA-9664981] Phosphorylated heterodimers of ERBB2 KD mutants:p-Y349,Y350-SHC1:GRB2:SOS1 [plasma membrane]
precedingEvent	[Reaction:R-HSA-9664976] Phosphorylated heterodimers of ERBB2 KD mutants phosphorylate SHC1 - Homo sapiens
releaseDate	2019-12-10
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:9662685] Kancha, Rama Krishna, 2019-09-16
schemaClass	Reaction
species	[Species:48887] Homo sapiens
stId	R-HSA-9664983
summation	[Summation:9664984] For the following ERBB2 KD mutants that were shown to activa...
updateTrackers	[UpdateTracker:9835786] Update Tracker - [Reaction:9664983] Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1 - v85:[modifyText]

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(updatedInstance)	[UpdateTracker:9835786] Update Tracker - [Reaction:9664983] Phosphorylated heterodimers of ERBB2 KD mutants recruit GRB2:SOS1 through SHC1 - v85:[modifyText]
(precedingEvent)	[Reaction:R-HSA-9664991] RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants
(hasEvent)	[Pathway:R-HSA-9664565] Signaling by ERBB2 KD Mutants

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