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Details on Person PI3K bound to phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 converts PIP2 to PIP3

Class:Id	Reaction:9664664
_displayName	PI3K bound to phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 converts PIP2 to PIP3
_doRelease	TRUE
_timestamp	2019-11-12 18:15:43
authored	[InstanceEdit:9656339] Orlic-Milacic, Marija, 2019-07-31
catalystActivity	[CatalystActivity:9664662] 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity of p-ERBB2 KD mutants:NRG1/NRG2:p-10Y-ERBB3:PI3K [plasma membrane]
compartment	[Compartment:876] plasma membrane [Compartment:70101] cytosol
created	[InstanceEdit:9664661] Orlic-Milacic, Marija, 2019-10-26
disease	[Disease:1500689] cancer
edited	[InstanceEdit:9665760] Orlic-Milacic, Marija, 2019-11-01
entityFunctionalStatus	[EntityFunctionalStatus:9664668] gain_of_function of p-ERBB2 KD mutants:NRG1/NRG2:p-10Y-ERBB3:PI3K [plasma membrane]
input	[SimpleEntity:179856] PI(4,5)P2 [plasma membrane] [SimpleEntity:113592] ATP [cytosol]
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: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
modified	[InstanceEdit:9664670] Orlic-Milacic, Marija, 2019-10-26 [InstanceEdit:9664756] 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	PI3K bound to phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 converts PIP2 to PIP3
normalReaction	[Reaction:1250462] PIP2 to PIP3 conversion by PI3K bound to phosphorylated heterodimer of ERBB2 and ERBB3 [Homo sapiens]
output	[SimpleEntity:179838] PI(3,4,5)P3 [plasma membrane] [SimpleEntity:29370] ADP [cytosol]
precedingEvent	[Reaction:9664646] Phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 bind PI3K [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:9664665] R-HSA-9664664.2
summation	[Summation:9664663] For the ERBB3-binding ERBB2 KD mutants that were shown to a...
(hasEvent)	[Pathway:9664565] Signaling by ERBB2 KD Mutants [Homo sapiens]
(precedingEvent)	[Reaction:9664918] Phosphorylated heterodimers of ERBB2 KD mutants and EGFR bind GRB2:GAB1 [Homo sapiens]
(updatedInstance)	[_UpdateTracker:9835792] Update Tracker - [Reaction:9664664] PI3K bound to phosphorylated heterodimers of ERBB2 KD mutants and ERBB3 converts PIP2 to PIP3 - v85:[modifyText]
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