Download or read book The Mechanism of Fas Ligand-mediated Costimulation Through Reverse Signaling written by Mingyi Sun and published by . This book was released on 2007 with total page 104 pages. Available in PDF, EPUB and Kindle. Book excerpt: We next focused on identifying subdomains of the Fas Ligand cytoplasmic tail that are critical for mediating costimulation. Despite the normal surface expression and killing mediated by mutated Fas Ligand lacking amino acids 45-54 in the proline-rich region of the Fas Ligand cytomplasmic domain, this mutant fails to costimulate, inhibiting Akt and Erk1/2 activation and antigen-specific CD8+ T cell proliferation. We further demonstrate that two conserved casein kinase I binding sites in the Fas ligand cytoplasmic domain are critical for Fas ligand costimulation by regulating NFAT activation. These results comprise the first mechanistic analysis of a newly emerging group of costimulators, the TNF family. Our work sheds light on the molecular understanding of Fas ligand as a double-edged immunomodulator, and helps to resolve the question of how one molecule can mediate discrete biological consequences in the immune system.