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Notch receptors C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The canonical Notch signalling pathway has four type I transmembrane Notch receptors (Notch1-4) and five ligands (DLL1, 2 and 3, and Jagged 1-2). Each member of this highly conserved receptor family plays a unique role in cell-fate determination during embryogenesis, differentiation, tissue patterning, proliferation and cell death [2]. As the Notch ligands are also membrane bound, cells have to be in close proximity for receptor-ligand interactions to occur. Cleavage of the intracellular domain (ICD) of activated Notch receptors by γ-secretase is required for downstream signalling and Notch-induced transcriptional modulation [3,10,14,21]. This is why γ-secretase inhibitors can be used to downregulate Notch signalling and explains their anti-cancer action. One such small molecule is RO4929097 [7], although development of this compound has been terminated following an unsuccessful Phase II single agent clinical trial in metastatic colorectal cancer [18].

Aberrant Notch signalling is implicated in a number of human cancers [5,11,15,19], with demcizumab and tarextumab identified as antibody inhibitors of ligand:receptor binding [12].

Targets

Targets of relevance to immunopharmacology are highlighted in blue

notch receptor 1 C Show summary »

notch receptor 2 C Show summary » More detailed page

notch receptor 3 C Show summary » More detailed page

notch receptor 4 C Show summary »

Further reading

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References

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

Thiruma V. Arumugam, Christopher Sobey. Notch receptors. Accessed on 19/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=914.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Buneman OP, Cidlowski JA, Christopoulos A, Davenport AP, Fabbro D, Spedding M, Striessnig J, Davies JA; CGTP Collaborators. (2017) The Concise Guide to PHARMACOLOGY 2017/18: Overview. Br J Pharmacol. 174 Suppl 1: S1-S16.