Human Interaction Network Ontology

Last uploaded: June 27, 2014
Preferred Name

Signaling by NODAL

Synonyms
Definitions

Reviewed: Peng, C, 2011-08-24 Edited: May, B, 2011-01-23 Signaling by NODAL is essential for patterning of the axes of the embryo and formation of mesoderm and endoderm (reviewed in Schier 2009, Shen 2007). The NODAL proprotein is secreted and cleaved extracellularly to yield mature NODAL. Mature NODAL homodimerizes and can also form heterodimers with LEFTY1, LEFTY2, or CERBERUS, which negatively regulate NODAL signaling. NODAL also forms heterodimers with GDF1, which increases NODAL activity. NODAL dimers bind the NODAL receptor comprising a type I Activin receptor (ACVR1B or ACVR1C), a type II Activin receptor (ACVR2A or ACVR2B), and an EGF-CFC coreceptor (CRIPTO or CRYPTIC). After binding NODAL, the type II activin receptor phosphorylates the type I activin receptor which then phosphorylates SMAD2 and SMAD3 (R-SMADs). Phosphorylated SMAD2 and SMAD3 form hetero-oligomeric complexes with SMAD4 (CO-SMAD) and transit from the cytosol to the nucleus. Within the nucleus the SMAD complexes interact with transcription factors such as FOXH1 to activate transcription of target genes. Authored: May, B, 2011-01-23

ID

http://purl.obolibrary.org/obo/HINO_0026258

comment

Reviewed: Peng, C, 2011-08-24

Edited: May, B, 2011-01-23

Signaling by NODAL is essential for patterning of the axes of the embryo and formation of mesoderm and endoderm (reviewed in Schier 2009, Shen 2007). The NODAL proprotein is secreted and cleaved extracellularly to yield mature NODAL. Mature NODAL homodimerizes and can also form heterodimers with LEFTY1, LEFTY2, or CERBERUS, which negatively regulate NODAL signaling. NODAL also forms heterodimers with GDF1, which increases NODAL activity. NODAL dimers bind the NODAL receptor comprising a type I Activin receptor (ACVR1B or ACVR1C), a type II Activin receptor (ACVR2A or ACVR2B), and an EGF-CFC coreceptor (CRIPTO or CRYPTIC). After binding NODAL, the type II activin receptor phosphorylates the type I activin receptor which then phosphorylates SMAD2 and SMAD3 (R-SMADs). Phosphorylated SMAD2 and SMAD3 form hetero-oligomeric complexes with SMAD4 (CO-SMAD) and transit from the cytosol to the nucleus. Within the nucleus the SMAD complexes interact with transcription factors such as FOXH1 to activate transcription of target genes.

Authored: May, B, 2011-01-23

definition source

Pubmed17287255

Reactome, http://www.reactome.org

Pubmed20066122

label

Signaling by NODAL

located_in

http://purl.obolibrary.org/obo/NCBITaxon_9606

prefixIRI

HINO:0026258

prefLabel

Signaling by NODAL

seeAlso

Reactome Database ID Release 431181150

ReactomeREACT_111057

subClassOf

http://purl.obolibrary.org/obo/INO_0000021

has_part

http://purl.obolibrary.org/obo/HINO_0026259

http://purl.obolibrary.org/obo/HINO_0017468

http://purl.obolibrary.org/obo/HINO_0017467

http://purl.obolibrary.org/obo/HINO_0022330

http://purl.obolibrary.org/obo/HINO_0017406

http://purl.obolibrary.org/obo/HINO_0017409

http://purl.obolibrary.org/obo/HINO_0017407

http://purl.obolibrary.org/obo/HINO_0019761

http://purl.obolibrary.org/obo/HINO_0019762

http://purl.obolibrary.org/obo/HINO_0017410

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