Fas Ligand 蛋白, Human (HEK293, His)

Fas Ligand (CD178; APTL) is a ligand to TNFRSF6/FAS/CD95, transduces the apoptotic signal to regulate cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development^[1]. Human Fas Ligand exhibits 4 isoforms, the soluble form (130-281 a.a.) of which plays an important role in the activation-induced cell death (AICD) of T lymphocytes Jurkat cells^[3]. However the membrane-bound isoform could be responsible for its inflammatory activity^[4]. Fas Ligand Protein, Human (HEK293, His) has a total length of 148 amino acids (P134-L281), is expressed in HEK392 cells with N-terminal 6*His-tag.

Fas Ligand (FasL；FASLG；CD95L) 是属于肿瘤坏死因子 (TNF) 的 TNFRSF6/FAS 的配体。FasL 是一种 II 型跨膜蛋白，可引发淋巴细胞凋亡^[1]。
FasL 在多种细胞类型上表达，包括 T 细胞、自然杀伤 (NK) 细胞、单核细胞、中性粒细胞、乳腺上皮细胞和血管内皮细胞^[3]。
FasL 裂解成 4 种亚型，包括膜型、可溶型、ADAM10 加工的 FasL 型 (APL)，发挥不同的生物活性和 SPPL2A 处理的 FasL 形式 (SPA)。其中，膜结合型和基质金属蛋白酶（MMP）蛋白水解作用产生的可溶型^[3]。
FasL或可溶性FasL与Fas结合导致受体聚集，导致Fas 相关死亡结构域的蛋白质与 Fas 细胞质尾部的相互作用。这种相互作用会触发一系列细胞内事件，包括激活类似 IL-1 转换酶的半胱氨酸蛋白酶 (Caspase 8)，最终导致核蛋白裂解、DNA 片段化和细胞凋亡^{[6].
鼠类 FasL、鼠类 Fas、人 Fas 或人 FasL 突变导致功能丧失，导致淋巴增殖、淋巴结病和自身免疫性疾病[1][3]}。
同时，缺陷性激活诱导细胞死亡 (AICD) 会导致患有狼疮样自身免疫性疾病的小鼠中 Fas 和 FasL 基因自发突变^[3]。
Human Fas Ligand 也参与 Jurkat 细胞凋亡，并结合 TNFRSF6B/DcR3 来阻止细胞凋亡，这是细胞凋亡终止的诱饵受体^[3]。
FasL 广泛存在于不同动物的序列不同，而人类与大鼠和小鼠的序列不同，相似度分别为 77.26% 和 78.06%。

Human soluble FasL (4000 units/mL; 18 hr) induces neutrophil infiltration^[4].
Human membrane-bound FasL (4000 units/mL; 18 hr) is found to induce IL-1β release in plastic adherent macrophages separated from 4-day PEC instead of recombinant mouse soluble FasL (WX1)^[4].
Soluble FasL (0.1-10 nM) of human induces chemotaxis of mouse neutrophils in vitro at concentrations incapable of inducing cell apoptosis.^[6].

Purified human soluble FasL (0-10 ng; i.p.; single dose) does not show neutrophil chemotactic activity in vivo in ddY mice^[4].
Expressing membrane-bound FasL (FFL, FDC2) but not soluble FasL (FFS) rejects tumor cells quickly than the control in wild-type mice^[4].

Loaded Human FAS-Fc on Protein A Biosensor, can bind Human Fas Ligand-His with an affinity constant of 2.82 nM as determined in BLI assay. 

Human

HEK293

N-6*His

P48023 (P134-L281)

356  [NCBI]

PSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGGLVINETGLYFVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWARSSYLGAVFNLTSADHLYVNVSELSLVNFEESQTFFGLYKL

20-30 kDa

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

溶液

Supplied as a 0.2 μm filtered solution of PBS, pH 7.4.

<1 EU/μg, determined by LAL method.

N/A.

Stored at -80°C for 1 year. It is stable at -20°C for 3 months after opening. It is recommended to freeze aliquots at -80°C for extended storage. Avoid repeated freeze-thaw cycles.

Shipping with dry ice.

• [1]. Schneider P, et al. Characterization of Fas (Apo-1, CD95)-Fas ligand interaction. J Biol Chem. 1997 Jul 25;272(30):18827-33.  [Content Brief]

  [2]. Liu W, et al. Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3. Structure. 2016 Nov 1;24(11):2016-2023.  [Content Brief]

  [3]. Martínez-Lorenzo MJ, et al. Release of preformed Fas ligand in soluble form is the major factor for activation-induced death of Jurkat T cells. Immunology. 1996 Dec;89(4):511-7.  [Content Brief]

  [4]. Shudo K, et al. The membrane-bound but not the soluble form of human Fas ligand is responsible for its inflammatory activity. Eur J Immunol. 2001 Aug;31(8):2504-11.  [Content Brief]

  [5]. Puppo F, et al. Fas, Fas ligand, and transfusion immunomodulation. Transfusion. 2001 Mar;41(3):416-8.  [Content Brief]

  [6]. Ottonello L, et al. Soluble Fas ligand is chemotactic for human neutrophilic polymorphonuclear leukocytes. J Immunol. 1999 Mar 15;162(6):3601-6.  [Content Brief]