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Notch受體與配體

Notch信號通路在生物體內扮演著至關重要的角色,不僅調控胚胎發育和成體組織穩態,更在多種癌癥的發生、發展中發揮雙重作用——既可作為腫瘤抑制因子,也能驅動癌細胞增殖、血管生成及免疫逃逸。本專題頁面系統梳理Notch1–4受體與DLL/JAG配體的核心知識,助您快速定位高品質重組蛋白、抗體及ELISA試劑盒,推進腫瘤及其他疾病領域的Notch相關研究。

Notch信號通路概覽

Notch信號通路是進化上高度保守的細胞間通訊系統,最早因果蠅翅膀“缺刻”表型而被發現。在哺乳動物中,該通路由4種跨膜受體(Notch1–4)和5種經典配體(DLL1、DLL3、DLL4、JAG1、JAG2)組成,僅在相鄰細胞直接接觸時被激活,精準調控細胞命運決定、分化、增殖及組織穩態。

所有Notch受體均為I型跨膜蛋白,在高爾基體中經furin酶切后以異二聚體形式定位于細胞膜;配體同樣為跨膜蛋白,表達于鄰近細胞表面。當配體與受體結合后,觸發兩次蛋白水解切割(ADAM介導的S2切割和γ-secretase介導的S3切割),釋放具有轉錄活性的Notch胞內結構域(NICD)。NICD進入細胞核,與RBP-J等因子形成轉錄復合物,激活Hes/Hey等靶基因表達,從而傳遞信號。

NOTCH信號通路示意圖

圖 NOTCH信號通路 [1]

(A. 配體結構特征;B. 受體結構特征;C. 信號接收與轉導過程。)

盡管通路機制高度相似,不同Notch受體與配體在組織分布、結合偏好及生物學功能上存在顯著差異——例如DLL4-Notch1主導血管生成,JAG1-Notch2參與腎臟發育,而DLL3則在小細胞肺癌中異常高表達。這些特異性決定了研究中靶點選擇與試劑匹配的重要性。

Notch受體與配體特性介紹

Notch信號通路的功能多樣性,源于其受體與配體在不同組織和發育階段的差異表達,以及由此產生的信號輸出特異性。下表匯總了四種Notch受體與五種經典配體的表達特征、核心生物學功能及相關的疾病背景,為您提供快速參考。

● Notch受體家族(Notch1-4)

靶點 主要表達部位 核心生物學功能 疾病關聯
Notch1 胸腺T細胞、血管內皮、神經前體細胞、乳腺上皮 T細胞發育、血管生成、干細胞維持 T細胞急性淋巴細胞白血病(T-ALL)[2,3]、乳腺癌 [4]、黑色素瘤 [5]、肝細胞癌 [6]、結直腸癌 [7]、阿爾茨海默病 [20]
Notch2 腎小管上皮、肝膽管細胞、B細胞、骨髓基質 腎臟/膽管發育、B細胞分化、肝再生 慢性淋巴細胞白血病(B-CLL )[8]、小細胞肺癌 [9]、胰腺癌 [10]、乳腺癌 [11]、Hajdu-Cheney綜合征 [18]、Alagille綜合征 [19]
Notch3 血管平滑肌細胞、腦小動脈、周細胞 血管平滑肌穩態、神經血管功能 遺傳性腦小血管病(CADASIL)[12]
Notch4 血管內皮、乳腺上皮 乳腺上皮發育、內皮屏障功能 系統性硬皮病 [13]、黑色素瘤 [14]、肝細胞癌 [15]、哮喘 [16]、雙相情感障礙 [17]

● Notch配體家族(DLL/JAG)

靶點 主要表達部位 核心生物學功能 疾病關聯
DLL1 神經干細胞、體節、造血微環境、腸隱窩 神經發生、體節形成、造血干祖細胞調控 乳腺癌 [21]、神經母細胞瘤 [22]、多發性骨髓瘤 [22]
DLL3 神經內分泌組織、胎兒腦、小細胞肺癌(SCLC) 抑制經典Notch信號,調控神經內分泌命運 小細胞肺癌(SCLC) [24-26]、神經內分泌癌 [27]
DLL4 血管內皮“尖端細胞”、腫瘤相關內皮、胸腺上皮 血管出芽調控,限制內皮“尖端細胞”過度增殖 結直腸癌 [28]、乳腺癌 [29]、肺癌 [30]、腎癌 [31]、胃癌 [32]
JAG1 肝膽管上皮、腎小管、心內膜、肝星狀細胞、腫瘤相關成纖維細胞 器官發育(肝/腎/心)、免疫調節、纖維化 Alagille綜合征 [33]、腎纖維化 [34]、三陰性乳腺癌 [35]
JAG2 骨細胞、胎盤滋養層細胞、T細胞、心臟瓣膜 骨發育、T細胞耐受 結直腸癌 [36]、多發性骨髓瘤 [37]、肺癌 [38]

熱門靶點聚焦

DLL3:小細胞肺癌的明星靶點

DLL3在超過80%的小細胞肺癌(SCLC)中高表達,且幾乎不在正常組織中出現,使其成為理想的腫瘤特異性抗原

機制特點:作為非典型配體,DLL3定位于高爾基體和細胞膜,通過反式抑制調控Notch信號,促進神經內分泌表型。
臨床進展:
  • ovalpituzumab tesirine(Rova-T):首個靶向DLL3的抗體偶聯藥物(ADC),雖在III期未達主要終點,但驗證了靶點可行性;
  • Tarlatamab(BiTE雙特異性T細胞銜接器):2024年獲FDA突破性療法認定,用于復發SCLC,客觀緩解率超40%;
  • 目前,多款靶向DLL3的雙特異性抗體、ADC藥物和CAR-T療法已進入臨床研究階段,展現出顯著治療潛力。

深入閱讀:DLL3靶點新突破:再鼎醫藥公布ZL-1310早期臨床數據!

查看所有DLL3相關產品

DLL4:調控腫瘤血管命運的關鍵開關

DLL4 在血管新生過程中發揮負調控作用——通過激活內皮細胞上的 Notch1 受體,抑制過度出芽,維持血管網絡的有序性。然而,在多種實體瘤(如乳腺癌、結直腸癌、肝癌)中,DLL4 異常高表達,導致腫瘤血管結構紊亂、灌注不足,反而促進缺氧、侵襲和免疫逃逸。

機制特點:靶向 DLL4 可誘導“非功能性血管增生”,雖增加血管密度,卻破壞其成熟性,加劇腫瘤內部缺氧并抑制生長。更值得關注的是,DLL4 抑制可重塑腫瘤免疫微環境,增強 T 細胞浸潤,與免疫檢查點抑制劑(如抗 PD-1)產生協同效應。
臨床進展:
  • 目前進展最快的 DLL4 靶向藥物是 Navicixizumab(OncoMed),一種 DLL4/VEGF 雙抗,已進入鉑耐藥卵巢癌的 III 期臨床試驗。

深入閱讀:DLL4:血管生成調控的關鍵靶點

查看所有DLL4相關產品

特色產品推薦

Notch 信號通路在發育、穩態及腫瘤等關鍵生物學過程中發揮核心調控作用,其深入研究離不開高特異性、高可靠性的實驗工具。華美生物提供覆蓋 Notch 全家族受體與配體的抗體、重組蛋白及 ELISA 試劑盒,助力您的科研精準高效推進。

● 部分數據展示

DLL3重組抗體

貨號:CSB-RA882142MA2HU

DLL3重組抗體ELISA圖

The Binding Activity of Human DLL3 with Anti-DLL3 recombinant antibody
Activity: Measured by its binding ability in a functional ELISA. Immobilized Human DLL3 (CSB-MP882142HU2d7) at 2 μg/mL can bind Anti-DLL3 recombinant antibody. The EC50 is 3.990-4.723 ng/mL.

DLL3重組抗體FC圖

SHP-77 cells were stained with Human IgG1&Igκ Isotype Control (CSB-RA011156MA1HU)(green line) and anti-DLL3 antibody (CSB-RA882142MA2HU) (2μg/1*106cells) (red line), washed and then followed by APC-conjugated anti-Human IgG Fc antibody and analyzed with flow cytometry.

DLL3重組抗體HPLC圖

The purity of DLL3 was greater than 95% as determined by SEC-HPLC

人DLL3重組蛋白

貨號:CSB-MP882142HU

DLL3重組蛋白SDS圖

(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.

DLL3重組蛋白AC圖

Activity: Measured by its binding ability in a functional ELISA. Immobilized DLL3 at 2 μg/ml can bind Anti-DLL3 Recombinant Antibody(CSB-RA882142A1HU), the EC50 is 1.102-1.707 ng/mL.

人DLL3 ELISA試劑盒

貨號:CSB-EL006948HU

DLL3 ELISA試劑盒標準曲線圖

These standard curves are provided for demonstration only. A standard curve should be generated for each set of samples assayed.

● 產品目錄

重組蛋白

Target Code Product Name Source
DLL3 CSB-EP882142HU Recombinant Human Delta-like protein 3 (DLL3), partial E.coli
DLL3 CSB-YP882142HU Recombinant Human Delta-like protein 3 (DLL3), partial Yeast
DLL3 CSB-EP882142HU1 Recombinant Human Delta-like protein 3 (DLL3), partial E.coli
DLL3 CSB-MP882142HU Recombinant Human Delta-like protein 3 (DLL3), partial (Active) Mammalian cell
DLL3 CSB-MP3536MOV Recombinant Macaca fascicularis Delta-like protein 3 (DLL3), partial (Active) Mammalian cell
DLL3 CSB-EP882142HU2-B Recombinant Human Delta-like protein 3 (DLL3), partial, Biotinylated E.coli
DLL3 CSB-MP882142HU2 Recombinant Human Delta-like protein 3 (DLL3), partial (Active) Mammalian cell
DLL3 CSB-MP882142HU2d7 Recombinant Human Delta-like protein 3 (DLL3), partial (Active) Mammalian cell
DLL3 CSB-MP882142HU3 Recombinant Human Delta-like protein 3 (DLL3), partial (Active) Mammalian cell
DLL3 CSB-MP882142HU3d7 Recombinant Human Delta-like protein 3 (DLL3), partial (Active) Mammalian cell
DLL4 CSB-MP878862HU Recombinant Human Delta-like protein 4 (DLL4), partial (Active) Mammalian cell
DLL4 CSB-MP7292MOV-C Recombinant Macaca fascicularis Delta-like protein (DLL4), partial Mammalian cell
Jag1 CSB-EP870758MO Recombinant Mouse Protein jagged-1 (Jag1), partial E.coli
JAG1 CSB-MP011927HUh6 Recombinant Human Protein jagged-1 (JAG1), partial Mammalian cell
NOTCH1 CSB-EP015949HU Recombinant Human Neurogenic locus notch homolog protein 1 (NOTCH1), partial E.coli
NOTCH2NLB CSB-BP3322HU Recombinant Human Notch homolog 2 N-terminal-like protein B (NOTCH2NLB) Baculovirus
NOTCH2NLB CSB-EP3322HU Recombinant Human Notch homolog 2 N-terminal-like protein B (NOTCH2NLB) E.coli

抗體

Target Code Product Name Tested Applications
DLL1 CSB-PA006947GA01HU DLL1 Antibody ELISA, WB
DLL3 CSB-RA882142MA2HU DLL3 Recombinant Monoclonal Antibody ELISA, FC
DLL3 CSB-PA882142LA01HU DLL3 Antibody ELISA, IHC
DLL3 CSB-PA882142LB01HU DLL3 Antibody, HRP conjugated ELISA
DLL3 CSB-PA882142LC01HU DLL3 Antibody, FITC conjugated
DLL3 CSB-PA882142LD01HU DLL3 Antibody, Biotin conjugated ELISA
DLL4 CSB-PA073786 DLL4 Antibody ELISA, IHC
DLL4 CSB-PA831848 DLL4 Antibody ELISA, IHC
DLL4 CSB-PA006949LA01HU DLL4 Antibody ELISA, IF
DLL4 CSB-PA006949LB01HU DLL4 Antibody, HRP conjugated ELISA
DLL4 CSB-PA006949LC01HU DLL4 Antibody, FITC conjugated
DLL4 CSB-PA006949LD01HU DLL4 Antibody, Biotin conjugated ELISA
JAG1 CSB-RA272247A0HU JAG1 Recombinant Monoclonal Antibody ELISA, IHC
JAG1 CSB-PA005638 JAG1 Antibody WB, ELISA
JAG1 CSB-PA969766 JAG1 Antibody ELISA, IHC
JAG1 CSB-PA234352 JAG1 Antibody ELISA, IHC
JAG1 CSB-PA01949A0Rb JAG1 Antibody ELISA, IHC, IF
JAG1 CSB-PA01949B0Rb JAG1 Antibody, HRP conjugated ELISA
JAG1 CSB-PA01949C0Rb JAG1 Antibody, FITC conjugated
JAG1 CSB-PA01949D0Rb JAG1 Antibody, Biotin conjugated ELISA

ELISA試劑盒

Target Code Product Name Detection Range Sensitivity
DLL1 CSB-EL006947HU Human Delta-like protein 1(DLL1) ELISA kit 31.25 pg/ml - 2000 pg/ml 7.8 pg/ml
DLL3 CSB-EL006948HU Human Delta-like protein 3(DLL3) ELISA kit 18.75 pg/mL-1200 pg/mL 4.68 pg/mL
DLL4 CSB-EL006949HU Human Delta-like protein 4(DLL4) ELISA kit 23.5 pg/mL-1500 pg/mL 5.8 pg/mL
DLL4 CSB-EL006949MO Mouse Delta-like protein 4(DLL4) ELISA kit 0.16 ng/ml-10 ng/ml 0.04ng/ml
JAG1 CSB-EL011927HU Human Protein jagged-1(JAG1) ELISA kit 0.156 ng/mL-10 ng/mL 0.039 ng/mL
NOTCH1 CSB-EL015949HU Human Neurogenic locus notch homolog protein 1(NOTCH1) ELISA kit 78 pg/mL-5000 pg/mL 19.5 pg/mL
NOTCH3 CSB-EL015952HU Human Neurogenic locus notch homolog protein 3(NOTCH3) ELISA kit 125 pg/mL-8000 pg/mL 31.25 pg/mL

參考文獻

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[29] Yan J,Xie Y,Liu Z, et al. DLL4-targeted CAR-T therapy sensitizes neoadjuvant chemotherapy via eliminating cancer stem cells and reshaping immune microenvironment in HER2 + breast cancer. J Immunother Cancer. 2024;12 (11):.

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[34] Li G,Liu B,Yang H, et al. Omega-3 polyunsaturated fatty acids alleviate renal fibrosis in chronic kidney disease by reducing macrophage activation and infiltration through the JAG1-NOTCH1/2 pathway. Int Immunopharmacol. 2025;152:114454.

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