Tumor necrosis factor receptor

The tumor necrosis factor receptor superfamily (TNFRSF) is a group of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha. In their active form, the majority of TNF receptors form trimeric complexes in the plasma membrame. Accordingly, most TNF receptors contain transmembrane domains (TMDs), although some can be cleaved into soluble forms (e.g. TNFR1), and some lack a TMD entirely (e.g. DcR3). In addition, most TNF receptors require specific adaptor protein such as TRADD, TRAF, RIP and FADD for downstream signalling. TNF receptors are primarily involved in apoptosis and inflammation, but they can also take part in other signal transduction pathways, such as proliferation, survival, and differentiation. TNF receptors are expressed in a wide variety of tissues in mammals, especially in leukocytes.

Death receptor 6

Death receptor 6 (DR6), also known as tumor necrosis factor receptor superfamily member 21 (TNFRSF21), is a cell surface receptor of the tumor necrosis factor receptor superfamily which activates the JNK and NF-κB pathways. It is mostly expressed in the thymus, spleen and white blood cells.

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been shown to activate NF-κB and MAPK8/JNK, and induce cell apoptosis. Through its death domain, this receptor interacts with TRADD protein, which is known to serve as an adaptor that mediates signal transduction of TNF-receptors. Knockout studies in mice suggested that this gene plays a role in T helper cell activation, and may be involved in inflammation and immune regulation.

Clinical significance

DR6 is also thought to be involved in neurodegeneration in the brain that causes Alzheimer's disease as well as signal transduction in stress response and cellular survival. DR6 induces apoptosis when it is over expressed, however the manner in which the death signal is intracellularly transduced is currently unknown. It has been determined that Bax translocation is necessary for the apoptosis triggered by DR6, but through an unknown pathway instead of the traditional pathways of intrinsic versus extrinsic. APP (amyloid precursor protein) is the natural ligand of DR6 and is first cleaved into Aβ and N-APP. N-APP is the fragment that interacts with DR6 to trigger axonal degradation in Alzheimer's patients. This pathway is essentially "hi-jacked" in the aging brain.

Death receptor 3

Death receptor 3 (DR3), also known as tumor necrosis factor receptor superfamily member 25 (TNFRSF25), is a cell surface receptor of the tumor necrosis factor receptor superfamily which mediates apoptotic signalling and differentiation. Its only known ligand is TNF-like protein 1A (TL1A).

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is expressed preferentially by activated and antigen-experienced T lymphocytes. TNFRSF25 is also highly expressed by FoxP3 positive regulatory T lymphocytes. TNFRSF25 is activated by a monogamous ligand, known as TL1A (TNFSF15), which is rapidly upregulated in antigen presenting cells and some endothelial cells following Toll-Like Receptor or Fc receptor activation. This receptor has been shown to signal both through the TRADD adaptor molecule to stimulate NF-kappa B activity or through the FADD adaptor molecule to stimulate caspase activation and regulate cell apoptosis.

R3

R3, R.III or R-3 or R/3 may refer to: