Reactome | JAG1 binds NOTCH2

JAG1 binds NOTCH2

Stable Identifier

R-HSA-1980056

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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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-NOTCH2 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).

NOTCHNLs, highly similar human-specific proteins encoded by Hominidae-specific NOTCH2NLA, NOTCH2NLB, and NOTCH2NLC genes that originate from the partial duplication of the NOTCH2 gene, stimulate NOTCH signaling (Fiddes et al. 2018, Suzuki et al. 2018) both in the presence and absence of the in trans DLL1, DLL4, and JAG2 ligands (Fiddes et al. 2018). JAG1 ligand was not directly studied in this context, but the regulation is inferred from the positive regulation of JAG2-stimulated NOTCH signaling. As a recombinant NOTCH2NLB was used in functional studies, NOTCH2NLB is annotated as a set member, while NOTCH2NLA and NOTCH2NLC are annotated as set candidates in this reaction showing the binding of JAG1 to NOTCH2. Although NOTCH1, NOTCH2, and NOTCH3 reporters were used to measure NOTCHNL-mediated activation of NOTCH signaling, the activity of NOTCH2NLs is only shown in the context of NOTCH2 signaling for several reasons. NOTCH2NLs are co-expressed with NOTCH2 due to promoter region of NOTCH2 being part of the duplicated segment (Fiddes et al. 2018, Suzuki et al. 2018), they likely act in cis, and are they are most similar in sequence to NOTCH2.

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
29856954	Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis Salama, SR, Dougherty, ML, Nowakowski, TJ, Haussler, D, Lorig-Roach, R, Bhaduri, A, Field, AR, Bishara, A, van den Bout, A, Addor, MC, Fiddes, IT, Bosworth, CM, Mooring, M, Lodewijk, GA, Katzman, S, Jacobs, FMJ, Kriegstein, A, Novak, AM, Ewing, AD, Mantalas, GL, Russo, L, Eichler, EE, Pollen, AA, Rosenkrantz, JL, Haeussler, M, Zwolinski, S, Nuttle, X	Cell	2018
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
29856955	Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis through Delta/Notch Regulation Polleux, F, Detours, V, Herpoel, A, Vanderhaeghen, P, Wojno, M, Kumar, D, Lambert, N, Suzuki, IK, Bilheu, A, Gacquer, D, Van Heurck, R, Cheron, J	Cell	2018
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