Cutting edge: two distinct motifs within the Fas ligand tail regulate Fas ligand-mediated costimulation.

نویسندگان

  • Mingyi Sun
  • Shinhee Lee
  • Saoussen Karray
  • Matthieu Levi-Strauss
  • Kristina T Ames
  • Pamela J Fink
چکیده

The cytoplasmic domain of Fas ligand is sufficient to costimulate CD8(+) T cells by driving Fas ligand recruitment into lipid rafts and association with select Src homology 3-containing proteins, activating PI3K and MAPK pathways, mediating nuclear translocation of the transcription factors NFAT and AP-1, and enhancing IFN-gamma production and Ag-specific CD8(+) T cell proliferation. We now show that Fas ligand molecules lacking amino acids 45-54 in the proline-rich region of the cytoplasmic domain fail to costimulate but serve as effective death inducers. Death induction and costimulation by Fas ligand are therefore clearly separable functions. Further, upon Fas ligand-mediated costimulation, casein kinase I phosphorylates Fas ligand, in which two conserved casein kinase I binding sites regulate NFAT activation and costimulation. These results help resolve how one molecule can serve as a double-edged immunomodulator by directing discrete biological consequences.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Aqueous Humor Levels of Soluble Fas and Fas-ligand in Patients with Primary Open Angle and Pseudoex-foliation Glaucoma

Background: Glaucoma is one of the most common causes of blindness and is usually associated with elevated intraocular pressure. In patients with primary open angle glau-coma the number of trabecular meshwork cells is decreased. Death of the trabecular meshwork cells may be a result of apoptosis. Objective: To investigate the aqueous humor levels of soluble Fas (sFas) and Fas-Ligand (sFasL) in ...

متن کامل

The dual functions of fas ligand in the regulation of peripheral CD8+ and CD4+ T cells.

Although Fas ligand (FasL) is well characterized for its capacity to deliver a death signal through its receptor Fas, recent work demonstrates that FasL also can receive signals facilitating antigen (Ag)-specific proliferation of CD8(+) T cells. The fact that the gld mutation differentially influences the proliferative capacity of CD8(+) and CD4(+) T cells presented the intriguing possibility t...

متن کامل

Separate domains of the human fas ligand dictate self-association and receptor binding.

The Fas receptor rapidly induces apoptosis when activated by ligand binding or by cross-linking with anti-Fas antibody. The Fas ligand (FasL), a member of the tumor necrosis factor family of ligands, is a 40-kilodalton type II transmembrane protein which is cleaved to produce soluble ligand. Although the Fas-FasL interaction plays a critical role in peripheral T cell homeostasis and cytotoxic T...

متن کامل

Fas and tumor necrosis factor receptor-mediated cell death: similarities and distinctions

Fas antigen and two tumor necrosis factor receptors (TNFR), p55 and p75, are implicated in the triggering of cell death upon stimulation by natural ligands and specific monoclonal antibodies. However, the relative efficiency of each receptor, the mechanisms that regulate their function and the signaling pathways they employ, remain to be elucidated. In this study, fusion proteins, composed of t...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Journal of immunology

دوره 179 9  شماره 

صفحات  -

تاریخ انتشار 2007