DLL4 binds NOTCH2

Stable Identifier
R-HSA-1980051
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
DLL4 binds NOTCH2
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

DLL4, expressed on a neighboring cell, binds NOTCH2 receptor and activates NOTCH2 intracellular signaling. The study used recombinant NOTCH2 and DLL4, exogenously expressed in Chinese hamster ovary cells. The species origin of NOTCH2 and DLL4 is not specified in the manuscript by Ji et al. 2004. The impact of fringe-mediated modification of NOTCH2 on activation by DLL4 has not been examined.

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 DLL4 ligand (Fiddes et al. 2018). 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 DLL4 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
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
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
15569487 Function of Delta4 gene and its effects on 32D cell differentiation

Zhang, MH, Ji, CY, Zhao, JQ, Ma, DX, Cui, CS, Guo, NJ

Chin Med J (Engl) 2004
Participants
Input
Output
Entity On Other Cell
Participates
as an event of
This event is regulated
Positively by
Regulator
NOTCH2NLB,(NOTCH2NLA,NOTCH2NLC) [extracellular region] (Homo sapiens)
Orthologous Events
DLL4 binds NOTCH2 (Gallus gallus)
Authored
Orlic-Milacic, M  (2013-01-11)
Reviewed
Heide, M  (2024-10-22)
Ilagan, MXG  (2013-04-25)
Haw, R  (2013-01-14)
Boyle, S  (2013-04-25)
Created
Orlic-Milacic, M  (2011-11-09)
Cite Us!