JAG1 binds NOTCH2

Stable Identifier
Reaction [binding]
Homo sapiens
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JAG1, expressed on a neighboring cell, binds NOTCH2 and activates intracellular NOTCH2 signaling (Shimizu et al. 1999, Shimizu et al. 2000). In contrast to NOTCH1, where fringe-mediated modification reduces the affinity of JAG1 for NOTCH1, it seems that fringe-mediated modification of NOTCH2 extracellular domain enhances activation of NOTCH2 signaling by JAG1 (Hicks et al. 2000).

JAG1-NOTCH2 signaling axis is affected in Alagille syndrome (AGS), a dominant congenital disorder characterized by hepatic bile duct abnormalities, as well as craniofacial, heart and kidney defects (Alagille et al. 1975, Habib et al. 1987). AGS is predominantly caused by mutations in JAG1 (Oda et al. 1997, Li et al. 1997) and less frequently by mutations in NOTCH2 (McDaniell et al. 2006).

JAG1 and NOTCH2 are expressed in kidney glomeruli and JAG1-NOTH2 signaling plays an important role in kidney development, as shown in mice mutant for JAG1 or NOTCH2 or both (McCright et al. 2001, McCright et al. 2002).
Literature References
PubMed ID Title Journal Year
10958687 Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2

Kanda, Y, Kurokawa, M, Shimizu, K, Hirai, H, Kumano, K, Hamada, Y, Saito, T, Chiba, S, Hosoya, N

Mol Cell Biol 2000
10934472 Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2

Collazo, A, Johnston, SH, Hicks, C, Weinmaster, G, diSibio, G, Vogt, TF

Nat Cell Biol 2000
11861489 A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency

Gridley, T, McCright, B, Lozier, J

Development 2002
9207787 Mutations in the human Jagged1 gene are responsible for Alagille syndrome

Spinner, NB, Okajima, K, Meltzer, PS, Collins, FS, Genin, A, Oda, T, Chandrasekharappa, SC, Piccoli, DA, Elkahloun, AG, Krantz, ID, Pike, BL

Nat. Genet. 1997
803282 Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur

Odièvre, M, Gautier, M, Alagille, D, Dommergues, JP

J. Pediatr. 1975
11171333 Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation

Weinmaster, G, McCright, B, Shen, L, Lan, Y, Gao, X, Lozier, J, Gridley, T, Herzlinger, D, Maguire, M, Jiang, R

Development 2001
16773578 NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway

Krantz, ID, Sanchez-Lara, PA, Spinner, NB, Pai, A, Warthen, DM, Piccoli, DA, McDaniell, R

Am J Hum Genet 2006
3153318 Glomerular mesangiolipidosis in Alagille syndrome (arteriohepatic dysplasia)

Odièvre, M, Gubler, MC, Gautier, M, Alagille, D, Dommergues, JP, Hadchouel, M, Habib, R

Pediatr. Nephrol. 1987
9207788 Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1

Genin, A, Kuo, WL, Li, L, Piccoli, DA, Hood, L, Banta, AB, Trask, BJ, Collins, CC, Rand, EB, Costa, T, Spinner, NB, Qi, M, Pierpont, ME, Krantz, ID, Deng, Y, Cochran, J

Nat. Genet. 1997
10551863 Mouse jagged1 physically interacts with notch2 and other notch receptors. Assessment by quantitative methods

Yazaki, Y, Kanda, Y, Shimizu, K, Takahashi, T, Hirai, H, Kumano, K, Hamada, Y, Chiba, S, Hosoya, N

J Biol Chem 1999
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