CD40L/CD154/TRAP 蛋白, Human

CD40L (CD154; TRAP) is a ligand to CD40/TNFRSF5, acts function by generating a costimulatory signal that up-regulates IL-4 synthesis^[1]. CD40L is specifically expressed on activated CD4+ T-lymphocytes and involves in activation of NF-κB/MAPK pathway^[2][3]. CD40L also involves in B cell differentiation, maturation, and apoptosis^[4]. CD40L in human, cleaved into 2 chains of membrane form (1-261 a.a.) and soluble form (113-261 a.a.) which serves as a ligand for integrins (ITGA5:ITGB1 and ITGAV:ITGB3). CD40L/CD154/TRAP Protein, Human has a total length of 149 amino acids (M113-L261), is expressed in E. coli cells with tag free.

“CD40 配体（CD40L；CD154；TRAP）属于肿瘤坏死因子 (TNF) 家族，是 CD40/TNFRSF5 的配体，特异性表达于活化的 CD4+ T 淋巴细胞^[1]。
CD40L 是 B 细胞上的 II 型跨膜蛋白，触发 B 细胞分化、成熟和凋亡的重要信号^[4]。
CD40L 通过与 T 细胞交联发挥作用产生共刺激信号，从而与TCR/CD3连接和CD28共刺激一起增强IL4和IL10的产生，并促进干扰素-γ和TNF-α的产生^[1][4]。
CD40L 与抗原呈递细胞 (APC) 上的 CD40 结合，通过刺激 I-κB 激酶 (IKK) 激活 TNFR 相关因子 2 和 IKK2 依赖性通路)，增加 NF-κB DNA 结合和 p65 核转位。I-κB 激酶的激活导致 c-Jun N 末端激酶强烈激活以及 GST-I-κB 和 GST-p65 磷酸化^[2]。
CD40L 参与 MAPK 通路，强烈抑制 Bcl-6，诱导 Erk1/2、p38 和 Jnk1/2 磷酸化，并激活 NF-κB 介导的 IRF4^[3].
CD40L 还与多种整合素结合并通过其发出信号，其中包括 αvβ3 和 α5β1，它们与 CD40L 的三聚体界面结合。CD40L 在免疫反应中发挥重要作用，是炎症的主要靶点^[5]。
CD40L 广泛存在于不同动物中，而人类的序列与恒河猴高度相似(98.08%)，但与大鼠和小鼠有很大不同，相似度分别为 77.31% 和 77.69%。人体内的CD40L被切割成膜形式(1-261aa)和可溶性形式(113-261aa)的2条链，而可溶性形式是通过蛋白水解加工从膜形式衍生出来的。血小板中可溶性 CD40L 的释放部分受到 GP IIb/IIIa、肌动蛋白聚合和基质金属蛋白酶 (MMP) 抑制剂敏感途径^[6]的调节。

"CD40 Ligand (1 ng/mL; 24 hr) induces endothelial cell vascular cell adhesion molecule-1 (VCAM-1) expression. CD40 Ligand shows costimulation effect with IL-4 against VCAM-1^[7].
CD40 Ligand (1 ng/mL; 24 hr) combined with IL-4 enhances IL-6 and inhibits IL-8 production by HUVEC^[7].
CD40 Ligand (500 ng/mL; 72 hr) with 50 ng/mL IL-21 stimulates eripheral blood mononuclear cells (PBMCs) to secrete donor-specific antibodies (DSA)^[8].
"

CD40 Ligand (2.86 ng/mL or 2.09 ng/mL) has been demonstrated to be a mark of cardiovascular risk, while the level (2.86 ng/mL) in who subsequently developed myocardial infarction, stroke, or cardiovascular death (cases) is higher than control group (2.09 ng/mL)^[8].

1. Measured in a cell proliferation assay using human B cells (Ramos) in the presence of 10 ng/mL Human IL-4. The ED₅₀ this effect is 2.92 ng/mL, corresponding to a specific activity is 3.4247×10⁵ units/mg.
2.The ED₅₀ as determined by the dose-dependant stimulation of IL-12 & IL-8 induction by PMB (Peripheral Mononuclear) cells was found to be <20 μg/mL.

• 
  Measured by its binding ability in a functional ELISA. Immobilized Mouse TREM2, at 1 μg/mL (100 μL/well) can bind Anti-TREM2 Antibody, the ED₅₀ is 46.44 ng/mL, corresponding to a specific activity is 2.153×10⁴ units/mg.

Human

E. coli

Tag Free

P29965 (M113-L261)

959  [NCBI]

MQKGDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVNVTDPSQVSHGTGFTSFGLLKL

Approximately 16.44 kDa

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

无菌粉末.

Lyophilized from a 0.2 μm filtered solution of 50 mM Tris, 250 mM NaCl, pH 8.0.

<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]. Blotta MH, et al. Cross-linking of the CD40 ligand on human CD4+ T lymphocytes generates a costimulatory signal that up-regulates IL-4 synthesis. J Immunol. 1996 May 1;156(9):3133-40.  [Content Brief]

  [2]. Schwabe RF, et al. CD40 activates NF-kappa B and c-Jun N-terminal kinase and enhances chemokine secretion on activated human hepatic stellate cells. J Immunol. 2001 Jun 1;166(11):6812-9.  [Content Brief]

  [3]. Batlle A, et al. CD40 and B-cell receptor signalling induce MAPK family members that can either induce or repress Bcl-6 expression. Mol Immunol. 2009 May;46(8-9):1727-35.  [Content Brief]

  [4]. Mikolajczak SA, et al. The modulation of CD40 ligand signaling by transmembrane CD28 splice variant in human T cells. J Exp Med. 2004 Apr 5;199(7):1025-31.  [Content Brief]

  [5]. Takada YK, et al. Soluble CD40L activates soluble and cell-surface integrin αvβ3, α5β1, and α4β1 by binding to the allosteric ligand-binding site (site 2). J Biol Chem. 2021 Jan-Jun;296:100399.  [Content Brief]

  [6]. Pietravalle F, et al. Human native soluble CD40L is a biologically active trimer, processed inside microsomes. J Biol Chem. 1996 Mar 15;271(11):5965-7.  [Content Brief]

  [7]. Kotowicz K, et al. Biological function of CD40 on human endothelial cells: costimulation with CD40 ligand and interleukin-4 selectively induces expression of vascular cell adhesion molecule-1 and P-selectin resulting in preferential adhesion of lymphocytes. Immunology. 2000 Aug;100(4):441-8.  [Content Brief]

  [8]. Schönbeck U, et al. Soluble CD40L and cardiovascular risk in women. Circulation. 2001 Nov 6;104(19):2266-8.  [Content Brief]