DLL4, expressed on a neighboring cell, binds NOTCH2 recep...

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.