NFAT Pathway - CISMeF

Preferred Label : NFAT Pathway;

NCIt related terms : NFAT and Hypertrophy of the heart (Transcription in the broken heart);

Alternative definition : BIOCARTA: Hypertrophy associated with both hypertension and obstruction to ventricular outflow leads to pathologic cardiac growth and it is associated with increase morbidity and mortality. Symptomatic ventricular disease takes a growing toll on the health of nations. As other cardiovascular diseases such as stroke and myocardial infarction are in decline as causes of mortality, the heart failure problem becomes increasingly urgent. Congenital heart defects occur in 1% of live births and fetal heart malformations are implicated in many pregnancies that end in still-birth or spontaneous abortion. The current paradigm suggests that the heart adapts to excess of hemodynamic loading by compensatory hypertrophy, which under condition of persistent stress, over time evolves into dysfunction and myocardial failure. There is considerable evidence that direct effects of increased mechanical stress are sensed within the ventricular wall and that signal is critical for the generation of growth responses. Despite compelling statistics we still do not understand biochemically why heart defects are so prevalent. A single transcriptional regulator initially associated with the activation of the T-cells (NFATc4) has been shown to link genetic and environmental causes of one class of congenital heart disorders, birth defects involving valve and septum formation. Within the endocardium, specific inductive events appear to activate NF-ATc: it is localized to the nucleus only in endocardial cells that are adjacent to the interface with the cardiac jelly and myocardium, which are thought to give the inductive stimulus to the valve primordia. Treatment with FK506, a specific calcineurin inhibitor, prevents nuclear localization of NF-ATc4. Activated CaMK stimulates calcineurin, which than acts through NF-ATc4 in association with GATA4, to induce hypertrophy. A model for the proposed role of calreticulin in the regulation of cardiac development requires a myogenic signal from extracellular space to activate the production of IP3 that results in the release of Ca2 from ER under the regulation of calreticulin (CRT). Increased intracellular Ca2 binds to calmodulin (CaM) and activates calcineurin (CaN). CaN dephosphorylates NF-ATc4 that translocates to the nucleus. In the nucleus NF-AT forms complexes with the GATA-4 and other transcription factors leading to activation of transcription of genes (e.g., ANF, a-actin, b-myosin, TNFa, ET-1, Adss1) essential for cardiac development. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_nfatPathway;

Details

Origin ID

C39162;

UMLS CUI

C1513836;

Semantic type(s)
- Physiologic Function [UMLS semantic type]
has_gene_product_element
- 3-Phosphoinositide-Dependent Protein Kinase 1 [NCIt concept]
- Angiotensin-1 [NCIt concept]
- Angiotensinogen [NCIt concept]
- Atrial Natriuretic Factor [NCIt concept]
- CREB-Binding Protein [NCIt concept]
- Calreticulin [NCIt concept]
- Cardiotrophin-1 [NCIt concept]
- Casein Kinase I Isoform Alpha [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 1 [NCIt concept]
- Endothelin-1 [NCIt concept]
- Fibroblast Growth Factor 2 [NCIt concept]
- GTPase HRas [NCIt concept]
- Glycogen Synthase Kinase-3 Beta [NCIt concept]
- Heart- and Neural Crest Derivatives-Expressed Protein 2 [NCIt concept]
- Heparin-Binding EGF-Like Growth Factor [NCIt concept]
- Histone Deacetylase 5 [NCIt concept]
- Histone Deacetylase 9 [NCIt concept]
- Homeobox Protein Nkx-2.5 [NCIt concept]
- Insulin-Like Growth Factor I [NCIt concept]
- Leukemia Inhibitory Factor [NCIt concept]
- Mitogen-Activated Protein Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 14 [NCIt concept]
- Mitogen-Activated Protein Kinase 3 [NCIt concept]
- Mitogen-Activated Protein Kinase 8 [NCIt concept]
- Myocyte-Specific Enhancer Factor 2C [NCIt concept]
- Phosphatidylinositol 3-Kinase Regulatory Subunit Alpha [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Isoform [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma Isoform [NCIt concept]
- RAC-Alpha Serine/Threonine Kinase [NCIt concept]
- RAF Proto-Oncogene Serine/Threonine-Protein Kinase [NCIt concept]
- Serine/Threonine Protein Phosphatase 2B Catalytic Subunit Alpha Isoform [NCIt concept]
- Serine/Threonine Protein Phosphatase 2B Catalytic Subunit Beta Isoform [NCIt concept]
- Serine/Threonine Protein Phosphatase 2B Catalytic Subunit Gamma Isoform [NCIt concept]
- Son of Sevenless Homolog 1 [NCIt concept]
- Transcription Factor GATA-4 [NCIt concept]
- cAMP-Dependent Protein Kinase Type I-Alpha Regulatory Subunit [NCIt concept]
pathway_has_gene_element
- AGT wt Allele [NCIt concept]
- AKT1 wt Allele [NCIt concept]
- CALR wt Allele [NCIt concept]
- CREBBP wt Allele [NCIt concept]
- CSNK1A1 wt Allele [NCIt concept]
- CTF1 wt Allele [NCIt concept]
- EDN1 wt Allele [NCIt concept]
- FGF2 wt Allele [NCIt concept]
- GATA4 wt Allele [NCIt concept]
- GSK3B wt Allele [NCIt concept]
- HAND2 wt Allele [NCIt concept]
- HBEGF wt Allele [NCIt concept]
- HDAC5 wt Allele [NCIt concept]
- HDAC9 wt Allele [NCIt concept]
- HRAS wt Allele [NCIt concept]
- IGF1 wt Allele [NCIt concept]
- LIF wt Allele [NCIt concept]
- MAP2K1 wt Allele [NCIt concept]
- MAPK1 wt Allele [NCIt concept]
- MAPK14 wt Allele [NCIt concept]
- MAPK3 wt Allele [NCIt concept]
- MAPK8 wt Allele [NCIt concept]
- MEF2C wt Allele [NCIt concept]
- NKX2-5 wt Allele [NCIt concept]
- NPPA wt Allele [NCIt concept]
- PDPK1 wt Allele [NCIt concept]
- PIK3CA wt Allele [NCIt concept]
- PIK3CG wt Allele [NCIt concept]
- PIK3R1 wt Allele [NCIt concept]
- PPP3CA wt Allele [NCIt concept]
- PPP3CB wt Allele [NCIt concept]
- PPP3CC wt Allele [NCIt concept]
- PRKAR1A wt Allele [NCIt concept]
- RAF1 wt Allele [NCIt concept]
- SOS1 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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