Reactome | Signaling by ERBB4

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Signaling by ERBB4 Show undefined attributes

authored	[InstanceEdit:1972351] Orlic-Milacic, M, 2011-11-04 [InstanceEdit:9638819] Stern, David F, 2019-02-21
compartment	[Compartment:70101] cytosol [Compartment:984] extracellular region [Compartment:876] plasma membrane
created	[InstanceEdit:1236397] Orlic-Milacic, Marija, 2011-03-25
crossReference	[DatabaseIdentifier:12819465] BioModels Database:BIOMD0000000255 [DatabaseIdentifier:12819471] BioModels Database:BIOMD0000000175
dbId	1236394
displayName	Signaling by ERBB4
doi	10.3180/R-HSA-1236394.3
edited	[InstanceEdit:1972361] Matthews, L, 2011-11-07 [InstanceEdit:1972360] D'Eustachio, P, 2011-11-07 [InstanceEdit:9638824] Orlic-Milacic, Marija, 2019-03-05
eventOf	[Pathway:R-HSA-9006934] Signaling by Receptor Tyrosine Kinases - Homo sapiens
figure	[Figure:2291888] /figures/Pathway_Illustrations/ERBB4_72_oicr.png
hasDiagram	true
hasEHLD	false
hasEvent	[Reaction:R-HSA-1236398] ERBB4 binds NRGs or EGF-like ligands - Homo sapiens [Reaction:R-HSA-1250220] Homodimerization of ERBB4 - Homo sapiens [Reaction:R-HSA-1250315] Trans-autophosphorylation of ERBB4 homodimers - Homo sapiens [Reaction:R-HSA-1977959] ERBB4 forms heterodimers with EGFR - Homo sapiens [Reaction:R-HSA-1977958] ERBB4 forms heterodimers with ERBB3 - Homo sapiens [Reaction:R-HSA-9612593] ERBB4 binds DLG4 - Homo sapiens [Reaction:R-HSA-9612639] NRG2-activated ERBB4 binds GABA receptors through GABRA1 - Homo sapiens [Pathway:R-HSA-1250347] SHC1 events in ERBB4 signaling - Homo sapiens [Pathway:R-HSA-1250342] PI3K events in ERBB4 signaling - Homo sapiens [Pathway:R-HSA-1251985] Nuclear signaling by ERBB4 - Homo sapiens [Pathway:R-HSA-1253288] Downregulation of ERBB4 signaling - Homo sapiens
isInDisease	false
isInferred	false
lastUpdatedDate	2019-06-12
literatureReference	[LiteratureReference:1254429] Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation [LiteratureReference:1254427] Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2 [LiteratureReference:1247834] ErbB-3 and ErbB-4 function as the respective low and high affinity receptors of all Neu differentiation factor/heregulin isoforms [LiteratureReference:1254428] Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases [LiteratureReference:1254439] Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4 [LiteratureReference:1254437] Identification and characterization of novel spliced variants of neuregulin 4 in prostate cancer [LiteratureReference:1250222] Ligand discrimination in signaling through an ErbB4 receptor homodimer [LiteratureReference:1250122] Neuregulin-1 only induces trans-phosphorylation between ErbB receptor heterodimer partners [LiteratureReference:1250306] HER4-mediated biological and biochemical properties in NIH 3T3 cells. Evidence for HER1-HER4 heterodimers [LiteratureReference:1250297] System-wide investigation of ErbB4 reveals 19 sites of Tyr phosphorylation that are unusually selective in their recruitment properties [LiteratureReference:1248688] Identification of autophosphorylation sites of HER2/neu [LiteratureReference:1973954] The cellular response to neuregulins is governed by complex interactions of the erbB receptor family [LiteratureReference:1248733] Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions [LiteratureReference:1250369] A natural ErbB4 isoform that does not activate phosphoinositide 3-kinase mediates proliferation but not survival or chemotaxis [LiteratureReference:1252006] Tumor necrosis factor-alpha-converting enzyme is required for cleavage of erbB4/HER4 [LiteratureReference:1251998] Ectodomain cleavage of ErbB-4: characterization of the cleavage site and m80 fragment [LiteratureReference:1252005] gamma -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase [LiteratureReference:1253316] Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain [LiteratureReference:1254286] The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone [LiteratureReference:1254297] Prolactin and ErbB4/HER4 signaling interact via Janus kinase 2 to induce mammary epithelial cell gene expression differentiation [LiteratureReference:1254407] Coregulation of estrogen receptor by ERBB4/HER4 establishes a growth-promoting autocrine signal in breast tumor cells [LiteratureReference:1254249] WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus [LiteratureReference:1254250] Ligand-regulated association of ErbB-4 to the transcriptional co-activator YAP65 controls transcription at the nuclear level [LiteratureReference:1253338] WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function [LiteratureReference:1254404] The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells [LiteratureReference:1253272] The E3 ligase Aip4/Itch ubiquitinates and targets ErbB-4 for degradation [LiteratureReference:1253295] The E3 ubiquitin ligase WWP1 selectively targets HER4 and its proteolytically derived signaling isoforms for degradation [LiteratureReference:1973946] Nedd4 mediates ErbB4 JM-a/CYT-1 ICD ubiquitination and degradation in MDCK II cells [LiteratureReference:2029517] Heregulin-dependent delay in mitotic progression requires HER4 and BRCA1 [LiteratureReference:9612773] ErbB4 regulation of a thalamic reticular nucleus circuit for sensory selection [LiteratureReference:9612772] Gene expression profiling of ErbB receptor and ligand-dependent transcription [LiteratureReference:9612796] Erbb4 deletion from fast-spiking interneurons causes schizophrenia-like phenotypes [LiteratureReference:9612797] Neuregulin 1-ErbB4 signaling in the bed nucleus of the stria terminalis regulates anxiety-like behavior [LiteratureReference:9612798] Neuregulin 1 protects against ischemic brain injury via ErbB4 receptors by increasing GABAergic transmission [LiteratureReference:9612815] Neuregulin-activated ERBB4 induces the SREBP-2 cholesterol biosynthetic pathway and increases low-density lipoprotein uptake [LiteratureReference:9612835] Neuregulin 1/ErbB4 enhances synchronized oscillations of prefrontal cortex neurons via inhibitory synapses [LiteratureReference:9612834] Maintenance of GABAergic activity by neuregulin 1-ErbB4 in amygdala for fear memory [LiteratureReference:9612570] ErbB4 reduces synaptic GABAA currents independent of its receptor tyrosine kinase activity [LiteratureReference:9612826] Neuregulin-1/ErbB4 Signaling Regulates Visual Cortical Plasticity [LiteratureReference:9612831] Neuregulin-1 protects against neurotoxicities induced by Swedish amyloid precursor protein via the ErbB4 receptor [LiteratureReference:9638212] Secretase-dependent tyrosine phosphorylation of Mdm2 by the ErbB-4 intracellular domain fragment [LiteratureReference:9638209] Interactions of ErbB4 and Kap1 connect the growth factor and DNA damage response pathways [LiteratureReference:9638198] ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation [LiteratureReference:9638195] Interaction with ErbB4 promotes hypoxia-inducible factor-1? signaling [LiteratureReference:9638207] Constitutively active ErbB4 and ErbB2 mutants exhibit distinct biological activities [LiteratureReference:9638213] Phosphotyrosine interactome of the ErbB-receptor kinase family [LiteratureReference:9612239] Convergent and divergent cellular responses by ErbB4 isoforms in mammary epithelial cells
maxDepth	3
modified	[InstanceEdit:10914110] Weiser, Joel, 2026-03-16
name	Signaling by ERBB4
orthologousEvent	[Pathway:R-CFA-1236394] Signaling by ERBB4 - Canis familiaris [Pathway:R-DME-1236394] Signaling by ERBB4 - Drosophila melanogaster [Pathway:R-CEL-1236394] Signaling by ERBB4 - Caenorhabditis elegans [Pathway:R-GGA-1236394] Signaling by ERBB4 - Gallus gallus [Pathway:R-XTR-1236394] Signaling by ERBB4 - Xenopus tropicalis [Pathway:R-DRE-1236394] Signaling by ERBB4 - Danio rerio [Pathway:R-SSC-1236394] Signaling by ERBB4 - Sus scrofa [Pathway:R-BTA-1236394] Signaling by ERBB4 - Bos taurus [Pathway:R-RNO-1236394] Signaling by ERBB4 - Rattus norvegicus [Pathway:R-MMU-1236394] Signaling by ERBB4 - Mus musculus
releaseDate	2011-12-06
reviewStatus	[ReviewStatus:9821382] five stars
reviewed	[InstanceEdit:1979910] Harris, RC, 2011-11-11 [InstanceEdit:1979909] Zeng, F, 2011-11-11 [InstanceEdit:2104982] Earp HS, 3rd, 2012-02-20 [InstanceEdit:2104979] Misior, AM, 2012-02-20
revised	[InstanceEdit:9638819] Stern, David F, 2019-02-21 [InstanceEdit:9612642] Orlic-Milacic, Marija, 2018-06-28
schemaClass	Pathway
species	[Species:48887] Homo sapiens
stId	R-HSA-1236394
summation	[Summation:1257607] ERBB4, also known as HER4, belongs to the ERBB family of rec...
updateTrackers	[UpdateTracker:9777777] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v69:[addHasEvent, addLiteratureReference, modifyText, updateContainedPathway, updateContainedRLE] [UpdateTracker:9784780] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v53:[updateContainedPathway] [UpdateTracker:9783366] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v56:[updateContainedPathway] [UpdateTracker:9779512] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v65:[updateContainedPathway, updateContainedRLE, updateIndirectRLE] [UpdateTracker:9788789] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v40:[addLiteratureReference, modifyText, updateContainedPathway, updateIndirectRLE] [UpdateTracker:9782411] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v59:[updateContainedPathway] [UpdateTracker:9781677] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v60:[updateContainedPathway, updateIndirectRLE] [UpdateTracker:9779265] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v66:[addLiteratureReference, modifyText, updateContainedPathway, updateContainedRLE, updateIndirectRLE] [UpdateTracker:9782948] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v58:[updateContainedPathway] [UpdateTracker:9788425] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v42:[updateContainedPathway] [UpdateTracker:9787813] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v44:[updateIndirectRLE]

Referrals

(hasEvent)	[Pathway:R-HSA-9006934] Signaling by Receptor Tyrosine Kinases
(hasEncapsulatedEvent)	[Pathway:R-HSA-8939211] ESR-mediated signaling [Pathway:R-HSA-1257604] PIP3 activates AKT signaling [Pathway:R-HSA-5673001] RAF/MAP kinase cascade
(updatedInstance)	[UpdateTracker:9777777] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v69:[addHasEvent, addLiteratureReference, modifyText, updateContainedPathway, updateContainedRLE] [UpdateTracker:9784780] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v53:[updateContainedPathway] [UpdateTracker:9783366] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v56:[updateContainedPathway] [UpdateTracker:9779512] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v65:[updateContainedPathway, updateContainedRLE, updateIndirectRLE] [UpdateTracker:9788789] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v40:[addLiteratureReference, modifyText, updateContainedPathway, updateIndirectRLE] [UpdateTracker:9782411] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v59:[updateContainedPathway] [UpdateTracker:9781677] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v60:[updateContainedPathway, updateIndirectRLE] [UpdateTracker:9779265] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v66:[addLiteratureReference, modifyText, updateContainedPathway, updateContainedRLE, updateIndirectRLE] [UpdateTracker:9782948] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v58:[updateContainedPathway] [UpdateTracker:9788425] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v42:[updateContainedPathway] [UpdateTracker:9787813] Update Tracker - [Pathway:1236394] Signaling by ERBB4 - v44:[updateIndirectRLE]

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