Reactome | ERBB2 KD mutants trans-autophosphorylate

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ERBB2 KD mutants trans-autophosphorylate Show undefined attributes

authored	[InstanceEdit:9656339] Orlic-Milacic, Marija, 2019-07-31
catalystActivity	[CatalystActivity:9664599] protein tyrosine kinase activity of Heterodimers of ERBB2 KD mutants [plasma membrane]
category	transition
compartment	[Compartment:70101] cytosol [Compartment:876] plasma membrane [Compartment:984] extracellular region
created	[InstanceEdit:9664587] Orlic-Milacic, Marija, 2019-10-25
crossReference	[DatabaseIdentifier:12020745] Mondo:0004992
dbId	9664588
disease	[Disease:1500689] cancer
displayName	ERBB2 KD mutants trans-autophosphorylate
edited	[InstanceEdit:9665760] Orlic-Milacic, Marija, 2019-11-01
entityFunctionalStatus	[EntityFunctionalStatus:9664607] gain_of_function of Heterodimers of ERBB2 KD mutants [plasma membrane]
eventOf	[Pathway:R-HSA-9664565] Signaling by ERBB2 KD Mutants - Homo sapiens
followingEvent	[Reaction:R-HSA-9665034] Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind PLCG1 - Homo sapiens [Reaction:R-HSA-9664646] Phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 bind PI3K - Homo sapiens [Reaction:R-HSA-9664950] Phosphorylated heterodimers of ERBB2 KD mutants bind SHC1 - Homo sapiens [Reaction:R-HSA-9665000] Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:SOS1 - Homo sapiens
input	43 × [SimpleEntity:R-ALL-113592] ATP [cytosol] [DefinedSet:R-HSA-9664568] Heterodimers of ERBB2 KD mutants [plasma membrane]
isChimeric	false
isInDisease	true
isInferred	false
literatureReference	[LiteratureReference:9649397] Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib [LiteratureReference:9646435] Activating HER2 mutations in HER2 gene amplification negative breast cancer [LiteratureReference:9650832] Anti-tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations [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: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:9646758] Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification [LiteratureReference:9646647] Carboxyl group footprinting mass spectrometry and molecular dynamics identify key interactions in the HER2-HER3 receptor tyrosine kinase interface [LiteratureReference:9647026] An Acquired HER2^T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer [LiteratureReference:9664473] Mutational activation of ErbB2 reveals a new protein kinase autoinhibition mechanism [LiteratureReference:9646776] EXEL-7647 inhibits mutant forms of ErbB2 associated with lapatinib resistance and neoplastic transformation [LiteratureReference:9646445] Combined Blockade of Activating ERBB2 Mutations and ER Results in Synthetic Lethality of ER+/HER2 Mutant Breast Cancer [LiteratureReference:9665642] HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors [LiteratureReference:9665657] The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272
maxDepth	1
modified	[InstanceEdit:9830342] Matthews, Lisa, 2023-03-08
name	ERBB2 KD mutants trans-autophosphorylate
normalReaction	[Reaction:R-HSA-1963582] Trans-autophosphorylation of ERBB2 heterodimers
output	43 × [SimpleEntity:R-ALL-29370] ADP [cytosol] [DefinedSet:R-HSA-9664606] Phosphorylated heterodimers of ERBB2 KD mutants [plasma membrane]
precedingEvent	[Reaction:R-HSA-9664567] ERBB2 KD mutants heterodimerize - Homo sapiens
regulatedBy	[NegativeRegulation:9665329] Negative regulation by 'ERBB2 KD mutants:TKIs:ERBIN:HSP90:CDC37 [plasma membrane]' [NegativeRegulation:9665328] Negative regulation by 'ERBB2 KD mutants (trastuzumab sensitive):trastuzumab:ERBIN:HSP90:CDC37 [plasma membrane]'
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-9664588
summation	[Summation:9664586] The following ERBB2 KD mutants were shown to undergo trans-a...
updateTrackers	[UpdateTracker:9835752] Update Tracker - [Reaction:9664588] ERBB2 KD mutants trans-autophosphorylate - v85:[modifyText]

Referrals

(updatedInstance)	[UpdateTracker:9835752] Update Tracker - [Reaction:9664588] ERBB2 KD mutants trans-autophosphorylate - v85:[modifyText]
(hasEvent)	[Pathway:R-HSA-9664565] Signaling by ERBB2 KD Mutants
(precedingEvent)	[Reaction:R-HSA-9665034] Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind PLCG1 [Reaction:R-HSA-9664646] Phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 bind PI3K [Reaction:R-HSA-9664950] Phosphorylated heterodimers of ERBB2 KD mutants bind SHC1 [Reaction:R-HSA-9665000] Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:SOS1

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