GITRL (glucocorticoid-induced TNF-related ligand), also known as TL6 and AITRL (activation-inducible TNF-related ligand), is a member of the tumor necrosis factor superfamily (TNFSF18). GITRL is a single-pass type II transmebrane glycoprotein consisting of a 50 amino acid (aa) cytoplasmic domain, a 21-aa transmembrane domain (TM) and a 128aa extracellular domain (ECD).  GITRL is expressed on antigen presenting cells, CD4-CD8-double negative thymic precursors, vascular endothelial cells, neurons, and in the eye. Its expression is transiently up regulated by proinflammatory stimulation.  GITRL binding to its receptor GITR provides a co-stimulatory signal to activated T cells and NK cells. This interaction also induces reverse signaling in GITRL-expressing dendritic cells (DC) to suppress cellular activation through the same pathway induced by the immunosuppressant dexamethasone. GITRL binding to GITR can also function as costimulator to lower the threshold for T-cell activation and T-cell proliferation. GITRL is important for interactions between activated T-lymphocytes and endothelial cells.  GITRL promotes leukocyte adhesion to endothelial cells and regulates migration of monocytes from the splenic reservoir to sites of inflammation.  In the central nervous system, GITRL/GITR interactions enhance NGF-mediated neurite outgrowth from sympathetic neurons. The binding of GITRL to GITR on mouse Treg cells permits the reactivation of T cells from Treg-induced suppression, although this does not appear to occur in humans.   

GITRL (glucocorticoid-induced TNF-related ligand), also known as TL6 and AITRL (activation-inducible TNF-related ligand), is a member of the tumor necrosis factor superfamily (TNFSF18). GITRL is a single-pass type II transmebrane glycoprotein consisting of a 50 amino acid (aa) cytoplasmic domain, a 21-aa transmembrane domain (TM) and a 128aa extracellular domain (ECD).  GITRL is expressed on antigen presenting cells, CD4-CD8-double negative thymic precursors, vascular endothelial cells, neurons, and in the eye. Its expression is transiently up regulated by proinflammatory stimulation.  GITRL binding to its receptor GITR provides a co-stimulatory signal to activated T cells and NK cells. This interaction also induces reverse signaling in GITRL-expressing dendritic cells (DC) to suppress cellular activation through the same pathway induced by the immunosuppressant dexamethasone. GITRL binding to GITR can also function as costimulator to lower the threshold for T-cell activation and T-cell proliferation. GITRL is important for interactions between activated T-lymphocytes and endothelial cells.  GITRL promotes leukocyte adhesion to endothelial cells and regulates migration of monocytes from the splenic reservoir to sites of inflammation.  In the central nervous system, GITRL/GITR interactions enhance NGF-mediated neurite outgrowth from sympathetic neurons. The binding of GITRL to GITR on mouse Treg cells permits the reactivation of T cells from Treg-induced suppression, although this does not appear to occur in humans.   

  

Product Details

 

Gene Symbol: GITRL; TL6; AITRL; GITRL; TNLG2A; hGITRL; TNFSF18; UNQ149/PRO175

  

NCBI Gene ID: 8995

 

Uniprot Entry: Q9UNG2

 

Construct Details: The recombinant human GITRL-Fc is expressed as a 357-amino acid protein consisting of Gln72 - Ser199 region of GITRL (UniProt accession #Q9UNG2) and a C-terminal Fc from human IgG1, which exists as a dimer under non-reducing conditions.   

  

Source:  Human cells stably expressing GITRL-Fc growing in chemical-defined media with no animal components or antibiotics 

 

Deduced Amino Acid Sequence:

        10         20         30         40         50         60 

QLETAKEPCM AKFGPLPSKW QMASSEPPCV NKVSDWKLEI LQNGLYLIYG QVAPNANYND  

        70         80         90        100        110        120 

VAPFEVRLYK NKDMIQTLTN KSKIQNVGGT YELHVGDTID LIFNSEHQVL KNNTYWGIIL 

       130        140        150        160        170        180 

LANPQFISRT DKTHTCPPCP APELLGGPSV FLFPPKPKDT LMISRTPEVT CVVVDVSHED 

       190        200        210        220        230        240 

PEVKFNWYVD GVEVHNAKTK PREEQYNSTY RVVSVLTVLH QDWLNGKEYK CKVSNKALPA 

       250        260        270        280        290        300 

PIEKTISKAK GQPREPQVYT LPPSREEMTK NQVSLTCLVK GFYPSDIAVE WESNGQPENN 

       310        320        330        340        350 

YKTTPPVLDS DGSFFLYSKL TVDKSRWQQG NVFSCSVMHE ALHNHYTQKS LSLSPGK 

 

M.W.: Calculated molecular mass (kDa): 40.3; Estimated by SDS-PAGE under reducing condition (kDa): 45-50

 

Calculated PI: 7.22

 

Calculated Extinction Coefficient (M^-1 cm^-1, at 280nm): 61350

 

Purity: >95% judged by SDS-PAGE under reducing condition (see the gel image above, labeled as DTT "+")

 

Formulation: Supplied at 0.5 mg/ml in sterile PBS pH7.4 (carrier and preservative free).

 

Endotoxin Level: <0.1 EU per 1 μg of purified recombinant protein determined by the LAL method

 

Biological Activity: Binds to its receptor GITR-Fc (SKU# FCL0289B) by ELISA.

 

  

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

Restriction: This product is not transferable or re-sellable.  Customer obtain no right to transfer, assign, or sublicense its use rights, or to transfer, resell, package, or otherwise distribute the product, or to use the product for the benefit of any third party or for any commercial purpose.  Customer may only use the product in compliance with applicable local, state and federal laws, regulations and rules.  Customer may not directly or indirectly use the product or allow the transfer, transmission, export or re-export of all or any part of the product in violation of any export control law or regulation of the united states or any other relevant jurisdiction.  Your use of this product constitutes acceptance of the terms of this limited use agreement.  Please refer to our “terms & conditions” for details.  If you are not willing to accept the limitation of this agreement, G&P Biosciences will accept return of the product for a full/partial refund.

 

Storage

 

The product is shipped at 4°C. Upon receipt, centrifuge the product briefly before opening the vial. It is recommended to store small aliquots at the temperature below –20°C for long-term storage and the product is stable for 6 months. 

 

 

 

 

 

Use a manual defrost freezer and avoid repeated freeze-thaw cycles.

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

 

References

 

 

1. J. Biol. Chem. 274:6056 (1999)

2. Curr. Biol. 9:215 (1999)

3. Proc. Natl. Acad. Sci. 100:15059 (2003)

4. J. Immunol. 173:5008 (2004)

5. Crit. Rev. Immunol. 30:547 (2010).

 

 

 

Documentation

 

Product datasheet (pdf) can be downloaded here: FCL2523-PDS.pdf

 

 

 

Additional supporting documents, including COA and MSDS are available upon request.

 

 

 

FOR RESEARCH USE ONLY. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE IN HUMAN.

Restriction: This product is not transferable or re-sellable.  Customer obtain no right to transfer, assign, or sublicense its use rights, or to transfer, resell, package, or otherwise distribute the product, or to use the product for the benefit of any third party or for any commercial purpose.  Customer may only use the product in compliance with applicable local, state and federal laws, regulations and rules.  Customer may not directly or indirectly use the product or allow the transfer, transmission, export or re-export of all or any part of the product in violation of any export control law or regulation of the united states or any other relevant jurisdiction.  Your use of this product constitutes acceptance of the terms of this limited use agreement.  Please refer to our “terms & conditions” for details.  If you are not willing to accept the limitation of this agreement, G&P Biosciences will accept return of the product for a full/partial refund.