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Details on Person Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:GAB1

Class:Id	Reaction:9664918
_displayName	Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:GAB1
_doRelease	TRUE
_timestamp	2019-11-12 18:16:05
authored	[InstanceEdit:9656339] Orlic-Milacic, Marija, 2019-07-31
compartment	[Compartment:876] plasma membrane [Compartment:70101] cytosol
created	[InstanceEdit:9664916] Orlic-Milacic, Marija, 2019-10-28
disease	[Disease:1500689] cancer
edited	[InstanceEdit:9665760] Orlic-Milacic, Marija, 2019-11-01
entityFunctionalStatus	[EntityFunctionalStatus:9664928] gain_of_function of p-6Y-ERBB2 KD mutants:EGF:p-6Y-EGFR [plasma membrane]
input	[Complex:9664917] p-6Y-ERBB2 KD mutants:EGF:p-6Y-EGFR [plasma membrane] [Homo sapiens] [Complex:179849] GRB2:GAB1 [cytosol] [Homo sapiens]
isChimeric	FALSE
literatureReference	[LiteratureReference:9649397] Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib [LiteratureReference:9646787] Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2) [LiteratureReference:9646445] Combined Blockade of Activating ERBB2 Mutations and ER Results in Synthetic Lethality of ER+/HER2 Mutant Breast Cancer [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: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:9647026] An Acquired HER2^T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer [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 [LiteratureReference:9665642] HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors
modified	[InstanceEdit:9664929] Orlic-Milacic, Marija, 2019-10-28 [InstanceEdit:9665666] Orlic-Milacic, Marija, 2019-10-31 [InstanceEdit:9666039] Orlic-Milacic, Marija, 2019-11-01 [InstanceEdit:9666040] Orlic-Milacic, Marija, 2019-11-01 [InstanceEdit:9666041] Orlic-Milacic, Marija, 2019-11-01 [InstanceEdit:9666042] Orlic-Milacic, Marija, 2019-11-01 [InstanceEdit:9667512] Orlic-Milacic, Marija, 2019-11-12 [InstanceEdit:9830342] Matthews, Lisa, 2023-03-08
name	Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:GAB1
normalReaction	[Reaction:1306963] Binding of GRB2:GAB1 to p-ERBB2:p-EGFR [Homo sapiens]
output	[Complex:9664921] p-6Y-ERBB2 KD mutants:EGF:p-6Y-EGFR:GRB2:GAB1 [plasma membrane] [Homo sapiens]
precedingEvent	[Reaction:9664664] PI3K bound to phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 converts PIP2 to PIP3 [Homo sapiens] [Reaction:9664646] Phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 bind PI3K [Homo sapiens]
releaseDate	2019-12-10
reviewed	[InstanceEdit:9662685] Kancha, Rama Krishna, 2019-09-16
reviewStatus	[ReviewStatus:9821382] five stars
species	[Species:48887] Homo sapiens
stableIdentifier	[StableIdentifier:9664922] R-HSA-9664918.2
summation	[Summation:9664919] Many EGFR-binding ERBB2 KD mutants were shown to activate PI...
(hasEvent)	[Pathway:9664565] Signaling by ERBB2 KD Mutants [Homo sapiens]
(precedingEvent)	[Reaction:9664933] Phosphorylated heterodimers of ERBB2 KD mutants and EGFR, in complex with GRB2:GAB1, bind PI3K [Homo sapiens]
(updatedInstance)	[_UpdateTracker:9835712] Update Tracker - [Reaction:9664918] Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:GAB1 - v85:[modifyText]
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