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Notch信号通路研究必备：从结构到疾病，一文读懂
88 人阅读发布时间：2026-03-20 11:43
Notch信号通路在生物体内扮演着至关重要的角色，不仅调控胚胎发育和成体组织稳态，更在多种癌症的发生、发展中发挥双重作用——既可作为肿瘤抑制因子，也能驱动癌细胞增殖、血管生成及免疫逃逸。本专题页面系统梳理Notch1–4受体与DLL/JAG配体的核心知识，助您快速定位高品质重组蛋白、抗体及ELISA试剂盒，推进肿瘤及其他疾病领域的Notch相关研究。
Notch信号通路是进化上高度保守的细胞间通讯系统，最早因果蝇翅膀“缺刻”表型而被发现。在哺乳动物中，该通路由4种跨膜受体（Notch1–4）和5种经典配体（DLL1、DLL3、DLL4、JAG1、JAG2）组成，仅在相邻细胞直接接触时被激活，精准调控细胞命运决定、分化、增殖及组织稳态。
所有Notch受体均为I型跨膜蛋白，在高尔基体中经furin酶切后以异二聚体形式定位于细胞膜；配体同样为跨膜蛋白，表达于邻近细胞表面。当配体与受体结合后，触发两次蛋白水解切割（ADAM介导的S2切割和γ-secretase介导的S3切割），释放具有转录活性的Notch胞内结构域（NICD）。NICD进入细胞核，与RBP-J等因子形成转录复合物，激活Hes/Hey等靶基因表达，从而传递信号。
Notch信号通路是进化上高度保守的细胞间通讯系统，最早因果蝇翅膀“缺刻”表型而被发现。在哺乳动物中，该通路由4种跨膜受体（Notch1–4）和5种经典配体（DLL1、DLL3、DLL4、JAG1、JAG2）组成，仅在相邻细胞直接接触时被激活，精准调控细胞命运决定、分化、增殖及组织稳态。
所有Notch受体均为I型跨膜蛋白，在高尔基体中经furin酶切后以异二聚体形式定位于细胞膜；配体同样为跨膜蛋白，表达于邻近细胞表面。当配体与受体结合后，触发两次蛋白水解切割（ADAM介导的S2切割和γ-secretase介导的S3切割），释放具有转录活性的Notch胞内结构域（NICD）。NICD进入细胞核，与RBP-J等因子形成转录复合物，激活Hes/Hey等靶基因表达，从而传递信号。
图 NOTCH信号通路 [1]
（A. 配体结构特征；B. 受体结构特征；C. 信号接收与转导过程。）
尽管通路机制高度相似，不同Notch受体与配体在组织分布、结合偏好及生物学功能上存在显著差异——例如DLL4-Notch1主导血管生成，JAG1-Notch2参与肾脏发育，而DLL3则在小细胞肺癌中异常高表达。这些特异性决定了研究中靶点选择与试剂匹配的重要性。
Notch信号通路的功能多样性，源于其受体与配体在不同组织和发育阶段的差异表达，以及由此产生的信号输出特异性。下表汇总了四种Notch受体与五种经典配体的表达特征、核心生物学功能及相关的疾病背景，为您提供快速参考。
● Notch受体家族（Notch1-4）
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● Notch配体家族（DLL/JAG）
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DLL3在超过80%的小细胞肺癌（SCLC）中高表达，且几乎不在正常组织中出现，使其成为理想的肿瘤特异性抗原。
机制特点：作为非典型配体，DLL3定位于高尔基体和细胞膜，通过反式抑制调控Notch信号，促进神经内分泌表型。
临床进展：
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ovalpituzumab tesirine（Rova-T）：靶向DLL3的抗体偶联药物（ADC），虽在III期未达主要终点，但验证了靶点可行性； -
Tarlatamab（BiTE双特异性T细胞衔接器）：2024年获FDA突破性疗法认定，用于复发SCLC，客观缓解率超40%； -
目前，多款靶向DLL3的双特异性抗体、ADC药物和CAR-T疗法已进入临床研究阶段，展现出显著治疗潜力。
深入阅读：DLL3靶点新突破：再鼎医药公布ZL-1310早期临床数据！查看所有DLL3相关产品
DLL4 在血管新生过程中发挥负调控作用——通过激活内皮细胞上的 Notch1 受体，抑制过度出芽，维持血管网络的有序性。然而，在多种实体瘤（如乳腺癌、结直肠癌、肝癌）中，DLL4 异常高表达，导致肿瘤血管结构紊乱、灌注不足，反而促进缺氧、侵袭和免疫逃逸。
机制特点：靶向 DLL4 可诱导“非功能性血管增生”，虽增加血管密度，却破坏其成熟性，加剧肿瘤内部缺氧并抑制生长。更值得关注的是，DLL4 抑制可重塑肿瘤免疫微环境，增强 T 细胞浸润，与免疫检查点抑制剂（如抗 PD-1）产生协同效应。
临床进展：
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目前进展最快的 DLL4 靶向药物是 Navicixizumab（OncoMed），一种 DLL4/VEGF 双抗，已进入铂耐药卵巢癌的 III 期临床试验。
深入阅读：DLL4：血管生成调控的关键靶点
查看所有DLL4相关产品Notch 信号通路在发育、稳态及肿瘤等关键生物学过程中发挥核心调控作用，其深入研究离不开高特异性、高可靠性的实验工具。华美生物提供覆盖 Notch 全家族受体与配体的抗体、重组蛋白及 ELISA 试剂盒，助力您的科研精准高效推进。
● 部分数据展示
DLL3重组抗体
货号：CSB-RA882142MA2HU
人DLL3重组蛋白
货号：CSB-MP882142HU
人DLL3 ELISA试剂盒
货号：CSB-EL006948HU
● 产品目录
重组蛋白
抗体
ELISA试剂盒
参考文献：
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