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Details on Person RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants and EGFR

Class:Id	Reaction:9665009
_displayName	RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants and EGFR
_doRelease	TRUE
_timestamp	2019-11-12 18:16:45
authored	[InstanceEdit:9656339] Orlic-Milacic, Marija, 2019-07-31
catalystActivity	[CatalystActivity:9665008] guanyl-nucleotide exchange factor activity of p-6Y-ERBB2 KD mutants:EGF:p-6Y-EGFR:GRB2:SOS1 [plasma membrane]
compartment	[Compartment:70101] cytosol [Compartment:876] plasma membrane
created	[InstanceEdit:9665007] Orlic-Milacic, Marija, 2019-10-28
disease	[Disease:1500689] cancer
edited	[InstanceEdit:9665760] Orlic-Milacic, Marija, 2019-11-01
entityFunctionalStatus	[EntityFunctionalStatus:9665011] gain_of_function of p-6Y-ERBB2 KD mutants:EGF:p-6Y-EGFR:GRB2:SOS1 [plasma membrane]
input	[Complex:109796] p21 RAS:GDP [plasma membrane] [Homo sapiens] [SimpleEntity:29438] GTP [cytosol]
isChimeric	FALSE
literatureReference	[LiteratureReference:9646776] EXEL-7647 inhibits mutant forms of ErbB2 associated with lapatinib resistance and neoplastic transformation [LiteratureReference:9649397] Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib [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: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:9665225] Orlic-Milacic, Marija, 2019-10-30 [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	RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants and EGFR
normalReaction	[Reaction:1250498] RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and phosphorylated EGFR:ERBB2 heterodimers [Homo sapiens]
output	[Complex:109783] p21 RAS:GTP [plasma membrane] [Homo sapiens] [SimpleEntity:29420] GDP [cytosol]
precedingEvent	[Reaction:9665000] Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:SOS1 [Homo sapiens] [Reaction:9664588] ERBB2 KD mutants trans-autophosphorylate [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:9665012] R-HSA-9665009.2
summation	[Summation:9665010] The following EGFR-binding ERBB2 KD mutants that were shown ...
(hasEvent)	[Pathway:9664565] Signaling by ERBB2 KD Mutants [Homo sapiens]
(updatedInstance)	[_UpdateTracker:9835769] Update Tracker - [Reaction:9665009] RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 KD mutants and EGFR - v85:[modifyText]
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