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Notch signaling pathway definition: The series of molecular signals initiated by binding of an extracellular ligand to a Notch receptor on the surface of the target cell. [GOC:go_curators]
Notch Signaling Pathway definition: Notch is a large cell-surface receptor that is activated by contact with membrane-bound ligands on neighboring cells. The ligands that activate Notch include Delta and Serrate, and Lag-2 is a Notch ligand in C. elegans. Activation of Notch by binding with its ligand on the surface of neighboring cells is involved in several developmental pathways, helping to determine cell fate. Much of the early insight into Notch signaling was derived from genetic studies in Drosophila and C. elegans models. Three different proteolytic steps process the 300 kD precursor of mature Notch. One protease is a furin-like enzyme that cleaves Notch constitutively adjacent to the amino acid sequence RQRR in the extracellular domain. Another proteolytic step in Notch processing is carried out by TACE, also known as ADAM17. Binding of extracellular ligand to Notch also induces cleavage at the transmembrane region by a gamma-secretase activity that is dependent on presenilin-1. The exact identity of the polypeptide that catalyzes the gamma-secretase enzyme activity has been debated. Labeling of presenilin with irreversible gamma-secretase transition state inhibitors indicates that is itself in fact the site of protease activity. It has also been argued that the gamma secretase is not presenilin-1 itself, but another polypeptide that requires Notch for its activity and is distinct from Presenilin-1. Cleavage of Notch in the extracellular domain releases the Notch intracellular domain (NCID) which migrates into the nucleus where it associates with CSL transcription factors and acts as a transcriptional coactivator. The proteolytic processing of Notch resembles in several ways the proteolytic processing of amyloid precursor protein (APP) that is implicated in plaque formation in Alzheimer's disease, with TACE and Presenilin-1 implicated in proteolytic processing of both Notch and APP. (BioCarta)
 
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Publications
 

Evolutionary conservation of plant gibberellin signalling pathway components

Filip Vandenbussche et al.

BMC Plant Biology , 29 Nov 2007

The therapeutic potential of modulators of the Hedgehog-Gli signaling pathway

Barbara Stecca et al.

Journal of Biology , 2002

A modification of Representational Difference Analysis, with application to the cloning of a candidate in the Reelin signalling pathway

Anelia A Kuvbachieva et al.

BMC Molecular Biology , 24 Apr 2002

Release of sunflower seed dormancy by cyanide: cross-talk with ethylene signalling pathway

Krystyna Oracz et al.

Journal of Experimental Botany , 01 May 2008

The role of hypoxia-inducible signaling pathway in nickel carcinogenesis.

Konstantin Salnikow et al.

Environmental Health Perspectives , 01 Oct 2002

Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway

Lambert CJ Dorssers et al.

Breast Cancer Research , 2005

Asthma families show transmission disequilibrium of gene variants in the vitamin D metabolism and signalling pathway

Matthias Wjst et al.

Respiratory Research , 2006

Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1

Miguel Otero et al.

Arthritis Research & Therapy , 2005

Cbl Enforces an SLP76-dependent Signaling Pathway for T Cell Differentiation * S⃞

Y. Jeffrey Chiang et al.

The Journal of Biological Chemistry , 13 Feb 2009

Activation of the SPHK/S1P signalling pathway is coupled to muscarinic receptor-dependent regulation of peripheral airways

Melanie Pfaff et al.

Respiratory Research , 2005

621 further publications >>