Fas Ligand Protein, 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), is a ligand for TNFRSF6/FAS belonging to the tumor necrosis factor (TNF). FasL is a type II transmembrane protein, riggering apoptosis of lymphocytes^[1].
FasL is expressed on a variety of cell types, including T cells, natural killer (NK) cells, monocytes, neutrophils, breast epithelial cells, and vascular endothelial cells^[3].
FasL exerts different biological activity by cleaved into 4 isoforms including membrane form, soluble form, ADAM10-processed FasL form (APL) and SPPL2A-processed FasL form (SPA). Among them, the membrane-bound form and a soluble form generated by proteolytic action of matrix metalloproteinases (MMP)^[3].
FasL or soluble FasL binding to Fas results in receptor aggregation and in the interaction of a protein called Fas-associated death domain with the Fas cytoplasmic tail. The interaction triggers a cascade of intracellular events, including the activation of the IL-1-converting enzyme-like cysteine protease (caspase 8), that ultimately leads to nucleoprotein cleavage, DNA fragmentation, and cell apoptosis^[6].
The loss of function due to mutations in murine FasL, murine Fas, human Fas, or human FasL leads to lymphoproliferation, lymphadenopathy, and autoimmune diseases^[1][3].
Meanwhile, defective activation-induced cell death (AICD) results in spontaneous mutation of Fas and FasL genes in mice with lupus-like autoimmune disease^[3].
Human Fas Ligand also involves in Jurkat cell apoptosis and binds TNFRSF6B/DcR3 to bolck apoptosis, which is a decoy receptor of apoptosis termination^[3].
FasL is widely found in different animals, while the sequence in Human is different from Rat and Mouse with similarity of 77.26% and 78.06%, respectively.

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.

Solution

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]