TNF Receptors

The TNF receptors, commonly referred to as type I and type II with a molecular mass of 55-60 kDa and 75-80 kDa, respectively, share a cysteine-rich extracellular domain and a distinct transmembrane domain. Type I receptor is expressed in all cell types, whereas type II is expressed only by cells of the immune system and on endothelial cells. Most TNF signals are mediated through the type I receptor; the precise role of type II receptor is still unclear. The cytoplasmic domains of both receptors lack any enzymatic activity. The death domain present in the cytoplasmic portion of the type I receptor is known to recruit at least 20 different proteins to form a cascade leading to activation of various cellular responses including apoptosis, nuclear transcription factor NFkB, and c-Jun N-terminal kinase. Soluble forms of both types of TNF receptors, consisting of an extracellular domain, have been identified in in vitro cell culture conditioned media and in serum, urine, synovial fluids, and cerebral spinal fluids of patients with various diseases. The soluble form of the type II receptor has been approved for human use in rheumatoid arthritis.