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Type II Cytokine Receptor
Type II cytokine receptors, also commonly known as class II cytokine receptors, are transmembrane proteins that are expressed on the surface of certain cells. They bind and respond to a select group of cytokines including interferon type I, interferon type II, interferon type III. and members of the interleukin-10 family These receptors are characterized by the lack of a WSXWS motif which differentiates them from type I cytokine receptors. Structure Typically type II cytokine receptors are heterodimers or multimers with a high and a low affinity component. These receptors are related predominantly by sequence similarities in their extracellular portions that are composed of tandem Ig-like domains. The structures for the extracellular domains of the receptors for interferon types, I, II, and III are all known. Type II cytokine receptors are tyrosine-kinase-linked receptors. The intracellular domain of type II cytokine receptors is typically associated with a tyrosine kinase ...
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Transmembrane
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently undergo significant conformational changes to move a substance through the membrane. They are usually highly hydrophobic and aggregate and precipitate in water. They require detergents or nonpolar solvents for extraction, although some of them (beta-barrels) can be also extracted using denaturing agents. The peptide sequence that spans the membrane, or the transmembrane segment, is largely hydrophobic and can be visualized using the hydropathy plot. Depending on the number of transmembrane segments, transmembrane proteins can be classified as single-span (or bitopic) or multi-span (polytopic). Some other integral membrane proteins are called monotopic, meaning that they are also permanently attached to the membrane, but do not pass ...
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JAK-STAT Signaling Pathway
The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through the process of transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors (which bind the chemical signals). Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system. Structure of JAKs and STATs ''Main articles: JAKs and STATs'' There are four JAK proteins: JAK1, JAK2, JAK3 and TYK2. JAKs contains a FERM domain (approximately 400 residues), an SH2-related domain (approximately 100 residues), a kinase domain (approximately 250 residues) and a pseudokinase domain (a ...
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Interferon-gamma Receptor
The interferon-gamma receptor (IFNGR) protein complex is the heterodimer of two chains: IFNGR1 and IFNGR2. It binds interferon-γ, the sole member of interferon type II. Structure and function The human interferon-gamma receptor complex consists the heterodimer of two chains: IFNGR1 and IFNGR2. In unstimulated cells, these subunits are not preassociated with each other but rather associate through their intracellular domains with inactive forms of specific Janus family kinases (Jak1 and Jak2). Jak1 and Jak2 constitutively associate with IFNGR1 and IFNGR2, respectively. Binding of IFN-γ to IFNGR1 induces the rapid dimerization of IFNGR1 chains, thereby forming a site that is recognized by the extracellular domain of IFNGR2. The ligand-induced assembly of the complete receptor complex contains two IFNGR1 and two IFNGR2 subunits, which bring into close juxtaposition the intracellular domains of these proteins together with the inactive Jak1 and Jak2 kinases that they associ ...
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Interferon-alpha/beta Receptor
The interferon-α/β receptor (IFNAR) is a virtually ubiquitous membrane receptor which binds endogenous type I interferon (IFN) cytokines. Endogenous human type I IFNs include many subtypes, such as interferons-α, -β, -ε, -κ, -ω, and -ζ. Function Activation of various innate immune signaling pathways (TLR3, TLR4, TLR7, TLR8, TLR9, cGAS, RIG-I, MDA-5) leads to the rapid induction of type I IFNs due to their (mostly) intronless gene structure. The regulatory elements upstream of type I IFN genes differ, allowing differential transcription of type I IFNs in response to stimuli. In particular, IFNβ contains a κB regulatory site, whereas IFNα subtypes do not. Production of specific type I IFNs is usually limited to a small number of type I IFN subtypes. Once secreted, type I IFNs signal through IFNAR in a paracrine and autocrine manner. IFNAR is a heteromeric cell surface receptor composed of two subunits, referred to as the low affinity subunit, IFNAR1, and the high a ...
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Regulation Of Gene Expression
Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from Transcriptional regulation, transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network. Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed. Although as early as 1951, Barbara McClintock showed interaction between two genetic loci, Activator (''Ac'') and Dissociator (''Ds''), in the color f ...
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Epithelial Cells
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellular matrix. Epithelial tissues line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs. An example is the epidermis, the outermost layer of the skin. There are three principal shapes of epithelial cell: squamous (scaly), columnar, and cuboidal. These can be arranged in a singular layer of cells as simple epithelium, either squamous, columnar, or cuboidal, or in layers of two or more cells deep as stratified (layered), or ''compound'', either squamous, columnar or cuboidal. In some tissues, a layer of columnar cells may appear to be stratified due to the placement of the nuclei. This sort of tissue is called pseudostratified. All glands are made up of epithelia ...
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Interleukin 28
Interleukin-28 (IL-28) is a cytokine that comes in two isoforms, IL-28A and IL-28B, and plays a role in immune defense against viruses, including the induction of an "antiviral state" by turning on Mx proteins, 2',5'-oligoadenylate synthetase as well as ISGF3G (Interferon Stimulated Gene Factor 3). IL-28A and IL-28B belong to the type III interferon family of cytokines and are highly similar (in amino acid sequence) to IL-29. Their classification as Interferons is due to their ability to induce an antiviral state, while their additional classification as cytokines is due to their chromosomal location as well as the fact that they are encoded by multiple exons, as opposed to a single exon, as most type-I IFNs are. Discovery IL-28 was discovered in 2002 by Zymogenetics using a genomic screening process in which the entire human genome was scanned for putative genes. Once these genes were found, a second scan was performed to look specifically for cytokines. Both IL-28 and ...
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Interleukin-22
Interleukin-22 (IL-22) is protein that in humans is encoded by the ''IL22'' gene. Structure IL-22 is an α-helical cytokine. IL-22 binds to a heterodimeric cell surface receptor composed of IL-10R2 and IL-22R1 subunits. IL-22R is expressed on tissue cells, and it is absent on immune cells. Crystallization is possible if the N-linked glycosylation sites are removed in mutants of IL-22 bound with high-affinity cell-surface receptor sIL-22R1. The crystallographic asymmetric unit contained two IL-22-sIL-22R1 complexes. Function IL-22 is produced by several populations of immune cells at a site of inflammation. Producers are αβ T cells classes Th1 cell, Th1, Th22 and T helper 17 cell, Th17 along with γδ T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ..., NKT cell, N ...
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Interleukin-20
Interleukin 20 (IL20) is a protein that is in humans encoded by the ''IL20'' gene which is located in close proximity to the IL-10 gene on the 1q32 chromosome. IL-20 is a part of an IL-20 subfamily which is a part of a larger IL-10 family. IL-20 subfamily also includes other cytokines, including IL-19, IL-20, IL-22, IL-24, and IL-26. Members of the cytokine IL-20 subfamily form an important link between the immune system and epithelial tissues due to the fact that receptors for these cytokines are highly expressed on epithelial cells and are almost exclusively produced by cells of the immune system. IL-20 requires an IL-β-subunit receptor ( IL-20RB) for signaling, which can form a functional heterodimeric receptor with either the α-subunit of the IL-20 receptor (IL-20RA) or the α1-subunit of the IL-22 receptor (IL-22RA1). Both of these receptor variants allow efficient IL-20 signaling. Receptors for IL-20 are expressed in the skin, lungs, ovary, testes, and place ...
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Interleukin 10
Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti- inflammatory cytokine. In humans, interleukin 10 is encoded by the ''IL10'' gene. IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins. Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and Tyk2 respectively. Gene and protein structure The IL-10 protein is a homodimer; each of its subunits is 178-amino-acid long. IL-10 is classified as a class-2 cytokine, a set of cytokines including IL-19, IL-20, IL-22, IL-24 (Mda-7), IL-26 and interferons type-I (IFN-alpha, -beta, -epsilon, -kappa, -omega), type-II (IFN-gamma) and type-III (IFN-lambda, also known as IL-28A, IL-28B, and IL-29). Expression and synthesis In humans, IL-10 is encoded by the ''IL10'' gene, whic ...
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Interleukin-10
Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti- inflammatory cytokine. In humans, interleukin 10 is encoded by the ''IL10'' gene. IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins. Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and Tyk2 respectively. Gene and protein structure The IL-10 protein is a homodimer; each of its subunits is 178-amino-acid long. IL-10 is classified as a class-2 cytokine, a set of cytokines including IL-19, IL-20, IL-22, IL-24 (Mda-7), IL-26 and interferons type-I (IFN-alpha, -beta, -epsilon, -kappa, -omega), type-II (IFN-gamma) and type-III (IFN-lambda, also known as IL-28A, IL-28B, and IL-29). Expression and synthesis In humans, IL-10 is encoded by the ''IL10'' gene, whic ...
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Interferon
Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses. IFNs belong to the large class of proteins known as cytokines, molecules used for communication between cells to trigger the protective defenses of the immune system that help eradicate pathogens. Interferons are named for their ability to "interfere" with viral replication by protecting cells from virus infections. However, virus-encoded genetic elements have the ability to antagonize the IFN response contributing to viral pathogenesis and viral diseases. IFNs also have various other functions: they activate immune cells, such as natural killer cells and macrophages, and they increase host defenses by up-regulating antigen presentation by virtue of increasing the expression of major histocompatibility complex (M ...
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