Molecular, structural, and biological characteristics of the tumor necrosis factor ligand superfamily.
The tumor necrosis factor receptor superfamily at present consists of ten different transmembrane (type I) glycoproteins with characteristic limited sequence homology for the cysteine-rich repeats in the extracellular domain. In parallel the tumor necrosis factor ligand super-family has been recognized by discovery of ligands for all members of the receptor superfamily. These molecules are also transmembrane (type II) glycoproteins, with the exception of lymphotoxin-alpha which is the only entirely secreted protein of the tumor necrosis factor-like proteins. Several members of the ligand superfamily, including tumor necrosis factor and CD95L also exist in a biologically active soluble form. The tumor necrosis factor ligand superfamily contains at present ten different proteins. In addition, NGFR p75 binds to a second family of proteins (neurotrophins). These nerve growth factor-like dimeric soluble molecules are basic neurotrophic factors and the five members (NGF, BDNF, NT-3, NT-4, NT-5) are not related to the tumor necrosis factor superfamily ligands. The members of the tumor necrosis factor ligand superfamily (TNF, LT-alpha, LT-beta, CD27L, CD30L, CD40L, CD95L, 4-IBB, OX40L, TRAIL) share common biological activities, but some properties are shared by only some ligands, while others are unique. The diverse biological activities triggered through tumor necrosis factor receptors have been linked to the regulation of cellular activation, including immune responses and inflammatory reactions, but also with the pathology of a series of human diseases.
Department of Internal Medicine III, University of Ulm Medical Center, Germany.
H J
HJ
Gruss
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D053282:CD27 Ligand; D053285:CD30 Ligand; D023201:CD40 Ligand; D053222:Fas Ligand Protein; D006801:Humans; D008024:Ligands; D008233:Lymphotoxin-alpha / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D008958:Models, Molecular; D008967:Molecular Biology; D015394:Molecular Structure; D009414:Nerve Growth Factors / Q000502:physiology; D053278:OX40 Ligand; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D053282:CD27 Ligand; D053285:CD30 Ligand; C505771:CD70 protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008233:Lymphotoxin-alpha; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D053278:OX40 Ligand; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505714:TNFRSF9 protein, human; C505653:TNFSF10 protein, human; C089251:TNFSF4 protein, human; C505774:TNFSF8 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand