DLL1, expressed on the surface of a neighboring cell, bin...

DLL1, expressed on the surface of a neighboring cell, binds NOTCH2 and activates NOTCH2-mediated intracellular signaling (Shimizu et al. 2000). Modification of NOTCH2 extracellular domain by fringe enzymes enhances NOTCH2 activation by DLL1 (Hicks et al. 2000). Activation of NOTCH2 signaling by DLL1 may regulate regeneration and proliferation of renal tubules during acute kidney injury (Kobayashi et al. 2008).

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 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 describing the binding of DLL1 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.