4-1BB/TNFRSF9 蛋白, Human (163a.a, HEK293, His)

4-1BB (CD137; TNFRSF9), a receptor of TNFSF9/4-1BBL, belongs to the tumor necrosis factor (TNF) receptor superfamily^[1]. 4-1BB is helpful for T cell activation and development, and also induces peripheral mononuclear cell proliferation and migration to the tumor microenvironment^[2]. 4-1BB is also involved in enhancing Nrf2 and NF-κB pathway mediated apoptosis of endothelial cells^[3]. Human 4-1BB protein is a surface glycoprotein with a transmembrane domain (187-213 a.a.). 4-1BB/TNFRSF9 Protein, Human (163a.a, HEK293, His) is the extracellular part (L24-Q186) of 4-1BB protein, produced by HEK293 cells with C-terminal 6*His-tag.

4-1BB，由TNFRSF9（CD137，ILA）编码，属于肿瘤坏死因子（TNF）受体超家族。4-1BB是一种表面糖蛋白，在多种细胞中表达，例如T细胞、B细胞、自然杀伤（NK）细胞、树突状（DC）、嗜酸性粒细胞和肥大细胞；甚至多种肿瘤细胞如人类白血病细胞。广泛分布于血管平滑肌、肿瘤血管壁和肝细胞癌的肝组织中。4-1BB 优先选择 CD8+ 细胞，而不是 CD4+ 细胞。它提供共刺激信号并激活 CD8+ T 细胞的细胞毒性作用，并有助于形成记忆 T 细胞。最后，它促进免疫系统对抗肿瘤。此外，CD137 将 CD137L 与信号单核细胞结合，增加其存活、增殖并刺激其迁移和外渗。此外，它还诱导多种促炎因子的释放，导致炎症单核细胞涌入组织，形成炎症环境^[1]。具体来说，CD137通过上调Fra1的表达来促进单核细胞/巨噬细胞向肿瘤微环境的迁移。同时还促进单核细胞/巨噬细胞分化为破骨细胞，从而为乳腺癌细胞在骨中定植和生长提供有利的微环境。它为乳腺癌转移提供了一种有前景的治疗策略^[2]。此外，CD137 信号传导通过分别由 Nrf2 和 NF-κB 通路介导的促氧化和促炎症机制促进内皮细胞 (EC) 凋亡^[3]。4-1BB蛋白在人和小鼠体内的同源性较低，序列相似度为56.75%。

4-1BB (human; 1 μg/mL; 16 h) leads to induction of monocyte activation and induces Myc protein production^[4].
4-1BB (human; 1 μg/mL; 10 d) prolongs survival of peripheral monocytes and (1 μg/mL; 1 h) induces expression of M-CSF^[5].
4-1BB (human; 1.2-40 μg/mL; 7 d) exhibits nhancement of cell numbers dose-dependently^[6].

1.Loaded Human 4-1BB-His on HIS1K Biosensor, can bind Anti-Human CD137 mAb-Fc with an affinity constant of 25.5 nM as determined in BLI assay.
2.Immobilized Human 4-1BB-His at 10 μg/mL (100 μl/well) can bind Human 4-1BBL-Fc.The ED₅₀ of Human IL-23-His is 1.61 μg/mL.

Human

HEK293

C-6*His

Q07011 (L24-Q186)

3604  [NCBI]

LQDPCSNCPAGTFCDNNRNQICSPCPPNSFSSAGGQRTCDICRQCKGVFRTRKECSSTSNAECDCTPGFHCLGAGCSMCEQDCKQGQELTKKGCKDCCFGTFNDQKRGICRPWTNCSLDGKSVLVNGTKERDVVCGPSPADLSPGASSVTPPAPAREPGHSPQ

28-35 kDa

Greater than 95% as determined by reducing SDS-PAGE.

无菌粉末.

Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US;may vary elsewhere.

• [1]. Ye L, et al. CD137, an attractive candidate for the immunotherapy of lung cancer. Cancer Sci. 2020 May;111(5):1461-1467.  [Content Brief]

  [2]. Wilcox RA, et al. Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors. J Clin Invest. 2002 Mar;109(5):651-9.  [Content Brief]

  [3]. Jiang P, et al. CD137 promotes bone metastasis of breast cancer by enhancing the migration and osteoclast differentiation of monocytes/macrophages. Theranostics. 2019 May 9;9(10):2950-2966.  [Content Brief]

  [4]. Geng T, et al. CD137 Signaling Promotes Endothelial Apoptosis by Inhibiting Nrf2 Pathway, and Upregulating NF-κB Pathway. Mediators Inflamm. 2020 Jun 6;2020:4321912.  [Content Brief]

  [5]. Langstein J, et al. Comparative analysis of CD137 and LPS effects on monocyte activation, survival, and proliferation. Biochem Biophys Res Commun. 2000 Jun 24;273(1):117-22.  [Content Brief]

  [6]. Langstein J, et al. Identification of CD137 as a potent monocyte survival factor. J Leukoc Biol. 1999 Jun;65(6):829-33.  [Content Brief]

  [7]. Jiang D, et al. CD137 induces proliferation of murine hematopoietic progenitor cells and differentiation to macrophages. J Immunol. 2008 Sep 15;181(6):3923-32.  [Content Brief]