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).

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Overview

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The canonocal 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

notch 1 C Show summary »

notch 2 C Show summary » More detailed page

notch 3 C Show summary » More detailed page

notch 4 C Show summary »

Further reading

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References

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How to cite this family page

Database page citation:

Notch receptors. Accessed on 18/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=914.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Buneman OP, Catterall WA, Cidlowski JA, Davenport AP, Fabbro D, Fan G, McGrath JC, Spedding M, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Overview. Br J Pharmacol. 172: 5729-5743.