DLL1 binds NOTCH2

<p>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).</p><p>NOTCHNLs, highly similar human-specific proteins encoded by Hominidae-specific <i>NOTCH2NLA</i>, <i>NOTCH2NLB</i>, and <i>NOTCH2NLC</i> genes that originate from the partial duplication of the <i>NOTCH2</i> gene, stimulate NOTCH signaling (Fiddes et al. 2018, Suzuki et al. 2018) both in the presence and absence of the <i>in trans</i> 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 <i>NOTCH2</i> being part of the duplicated segment (Fiddes et al. 2018, Suzuki et al. 2018), they likely act <i>in cis</i>, and are they are most similar in sequence to NOTCH2.</p>

<p>DLL1蛋白，于邻近细胞表面表达，与NOTCH2蛋白结合并激活NOTCH2介导的细胞内信号传导（Shimizu等，2000年）。通过边缘酶对NOTCH2细胞外结构的修饰，可增强DLL1对NOTCH2的激活作用（Hicks等，2000年）。DLL1激活NOTCH2信号传导可能调节急性肾损伤期间肾小管的再生和增殖（Kobayashi等，2008年）。</p><p>NOTCHNLs，由人科特有基因<i>NOTCH2NLA</i>、<i>NOTCH2NLB</i>和<i>NOTCH2NLC</i>编码的高度相似的人特异蛋白，源自<i>NOTCH2</i>基因的部分复制，能够在存在和不存在<i>in trans</i> DLL1配体的情况下刺激NOTCH信号传导（Fiddes等，2018年，Suzuki等，2018年）。由于在功能研究中使用了重组的NOTCH2NLB，因此NOTCH2NLB被标注为集合成员，而NOTCH2NLA和NOTCH2NLC被标注为集合候选者在描述DLL1与NOTCH2结合的反应中。尽管使用了NOTCH1、NOTCH2和NOTCH3报告基因来测量NOTCHNL介导的NOTCH信号传导的激活，但NOTCH2NLs的活动仅在NOTCH2信号传导的背景下展示，原因有数。由于<i>NOTCH2</i>启动子区域是复制片段的一部分，因此NOTCH2NLs与NOTCH2共表达，它们可能以<i>in cis</i>方式作用，并且在序列上与NOTCH2最为相似（Fiddes等，2018年，Suzuki等，2018年）。</p>