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PI3K bound to phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 converts PIP2 to PIP3
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authored
[InstanceEdit:9656339] Orlic-Milacic, Marija, 2019年07月31日
catalystActivity
[CatalystActivity:9664662] 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity of p-ERBB2 KD mutants:NRG1/NRG2:p-10Y-ERBB3:PI3K [plasma membrane]
category
transition
compartment
[Compartment:876] plasma membrane
[Compartment:70101] cytosol
created
[InstanceEdit:9664661] Orlic-Milacic, Marija, 2019年10月26日
crossReference
[DatabaseIdentifier:12610421] Rhea:21292
[DatabaseIdentifier:11944892] Mondo:0004992
dbId
9664664
disease
[Disease:1500689] cancer
displayName
PI3K bound to phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 converts PIP2 to PIP3
edited
[InstanceEdit:9665760] Orlic-Milacic, Marija, 2019年11月01日
entityFunctionalStatus
[EntityFunctionalStatus:9664668] gain_of_function of p-ERBB2 KD mutants:NRG1/NRG2:p-10Y-ERBB3:PI3K [plasma membrane]
eventOf
[Pathway:R-HSA-9664565] Signaling by ERBB2 KD Mutants - Homo sapiens
followingEvent
[Reaction:R-HSA-9664918] Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:GAB1 - Homo sapiens
input
[SimpleEntity:R-ALL-113592] ATP [cytosol]
[SimpleEntity:R-ALL-179856] PI(4,5)P2 [plasma membrane]
isChimeric
false
isInDisease
true
isInferred
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: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: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
maxDepth
1
modified
[InstanceEdit:9830342] Matthews, Lisa, 2023年03月08日
name
PI3K bound to phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 converts PIP2 to PIP3
normalReaction
[Reaction:R-HSA-1250462] PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB3
output
[SimpleEntity:R-ALL-29370] ADP [cytosol]
[SimpleEntity:R-ALL-179838] PI(3,4,5)P3 [plasma membrane]
precedingEvent
[Reaction:R-HSA-9664646] Phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 bind PI3K - Homo sapiens
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-9664664
summation
[Summation:9664663] For the ERBB3-binding ERBB2 KD mutants that were shown to a...
updateTrackers
[UpdateTracker:9835792] Update Tracker - [Reaction:9664664] PI3K bound to phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 converts PIP2 to PIP3 - v85:[modifyText]
Referrals
(updatedInstance)
[UpdateTracker:9835792] Update Tracker - [Reaction:9664664] PI3K bound to phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 converts PIP2 to PIP3 - v85:[modifyText]
(hasEvent)
[Pathway:R-HSA-9664565] Signaling by ERBB2 KD Mutants
(precedingEvent)
[Reaction:R-HSA-9664918] Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:GAB1
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