RGD Reference Report - Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling.

Authors: Matsushima, Shouji  Kuroda, Junya  Zhai, Peiyong  Liu, Tong  Ikeda, Shohei  Nagarajan, Narayani  Oka, Shin-Ichi  Yokota, Takashi  Kinugawa, Shintaro  Hsu, Chiao-Po  Li, Hong  Tsutsui, Hiroyuki  Sadoshima, Junichi 
Citation: Matsushima S, etal., J Clin Invest. 2016 Sep 1;126(9):3403-16. doi: 10.1172/JCI85624. Epub 2016 Aug 15.
RGD ID: 13601987
Pubmed: PMID:27525436   (View Abstract at PubMed)
PMCID: PMC5004961   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI85624   (Journal Full-text)

NADPH oxidases (Noxes) produce ROS that regulate cell growth and death. NOX4 expression in cardiomyocytes (CMs) plays an important role in cardiac remodeling and injury, but the posttranslational mechanisms that modulate this enzyme are poorly understood. Here, we determined that FYN, a Src family tyrosine kinase, interacts with the C-terminal domain of NOX4. FYN and NOX4 colocalized in perinuclear mitochondria, ER, and nuclear fractions in CMs, and FYN expression negatively regulated NOX4-induced O2- production and apoptosis in CMs. Mechanistically, we found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation. Transverse aortic constriction activated FYN in the left ventricle (LV), and FYN-deficient mice displayed exacerbated cardiac hypertrophy and dysfunction and increased ROS production and apoptosis. Deletion of Nox4 rescued the exaggerated LV remodeling in FYN-deficient mice. Furthermore, FYN expression was markedly decreased in failing human hearts, corroborating its role as a regulator of cardiac cell death and ROS production. In conclusion, FYN is activated by oxidative stress and serves as a negative feedback regulator of NOX4 in CMs during cardiac remodeling.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FynRatmitochondrion located_inIDA PMID:27525436ARUK-UCL 
Nox4Ratmitochondrion located_inIDA PMID:27525436ARUK-UCL 
FynRatnucleus located_inIDA PMID:27525436ARUK-UCL 
Nox4Ratnucleus located_inIDA PMID:27525436ARUK-UCL 
FynRatperinuclear endoplasmic reticulum located_inIDA PMID:27525436ARUK-UCL 
Nox4Ratperinuclear endoplasmic reticulum located_inIDA PMID:27525436ARUK-UCL 
FynRatperinuclear region of cytoplasm located_inIDA PMID:27525436ARUK-UCL 
Nox4Ratperinuclear region of cytoplasm located_inIDA PMID:27525436ARUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Fyn  (FYN proto-oncogene, Src family tyrosine kinase)
Nox4  (NADPH oxidase 4)


Additional Information