Structure and function of Fas/Fas ligand.
Fas is a member of the TNF receptor family, that contain 2-6 cysteine-rich domains (CRDs) in their extracellular regions, a single transmembrane domain and variably sized intracytoplasmic domains. Fas belongs to a subgroup of family members that have a "death domain" near the carboxy-terminal region of the molecule. This domain binds to adaptor molecules that transmit a death signal to the cell. Signal transduction is complex and involves caspases, ceramides and stress pathways. Fas ligand is biologically active as a homotrimer. Receptor binding has been localized to the C-terminus and a self-association motif to the N-terminus of the ligand extracellular domain. Expression of ligand in a functionally active form is highly regulated at the transcriptional level as well as by cleavage by metalloproteinases. Since Fas/Fas ligand delete activated cells in the peripheral immune system, defects in this pathway predispose to autoimmune disorders.
Orlinick
J R
JR
Hospital for Special Surgery, Cornell University Medical Center, New York, NY 10021, USA.
Vaishnaw
A K
AK
Elkon
K B
KB
D000818:Animals; D017209:Apoptosis; D053222:Fas Ligand Protein; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D019014:fas Receptor / Q000737:chemistry / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor