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Entries
ERBB2 KD mutants trans-autophosphorylate
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authored
[InstanceEdit:9656339] Orlic-Milacic, Marija, 2019年07月31日
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年10月25日
crossReference
[DatabaseIdentifier:11944892] Mondo:0004992
dbId
9664588
disease
[Disease:1500689] cancer
displayName
ERBB2 KD mutants trans-autophosphorylate
edited
[InstanceEdit:9665760] Orlic-Milacic, Marija, 2019年11月01日
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年03月08日
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-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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