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JAK3
Tyrosine-protein kinase JAK3 is a tyrosine kinase enzyme that in humans is encoded by the ''JAK3'' gene. Janus kinases Janus kinase 3 is a tyrosine kinase that belongs to the janus family of kinases. Other members of the Janus family include JAK1, JAK2 and TYK2. Janus kinases (JAKs) are relatively large kinases of approximately 1150 amino acids with apparent molecular weights of 120-130 kDa. They are cytosolic tyrosine kinases that are specifically associated with cytokine receptors. Since cytokine receptor proteins lack enzymatic activity, they are dependent upon JAKs to initiate signaling upon binding of their ligands (e.g. cytokines). The cytokine receptors can be divided into five major subgroups based on their different domains and activation motifs. JAK3 is required for signaling of the type I receptors that use the common gamma chain (γc).Studies suggest Jak3 plays essential roles in immune and nonimmune cell physiology. Epithelial Jak3 is important for the regulation ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tofacitinib
Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. Common side effects include diarrhea, headache, and high blood pressure. Serious side effects may include infections, cancer, and pulmonary embolism. In 2019, the safety committee of the European Medicines Agency began a review of tofacitinib and recommended that doctors temporarily not prescribe the 10 mg twice-daily dose to people at high risk for pulmonary embolism. The U.S. Food and Drug Administration (FDA) also released warnings about the risk of blood clots. An important side effect of Jakinibs is serious bacterial, mycobacterial, fungal and viral infections. In the phase 3 trials of tofacitinib among opportunistic infections, pulmonary tuberculosis (TB) was reported in 3 cases all of which were initially negative upon screening for TB. It is a janus kinase (JAK) inhibitor, discovered and developed by the Nation ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TYK2
Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the ''TYK2'' gene. Tyk2 was the first member of the JAK family that was described (the other members are JAK1, JAK2, and JAK3). It has been implicated in IFN-α, IL-6, IL-10 and IL-12 signaling. Function This gene encodes a member of the tyrosine kinase and, to be more specific, the Janus kinases (JAKs) protein families. This protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promulgate cytokine signals by phosphorylating receptor subunits. It is also component of both the type I and type III interferon signaling pathways. As such, it may play a role in anti-viral immunity. Cytokines play pivotal roles in immunity and inflammation by regulating the survival, proliferation, differentiation, and function of immune cells, as well as cells from other organ systems. Hence, targeting cytokines and their receptors is an effective means of treating such dis ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Janus Kinase
Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 and 2 (since they were just two of many discoveries in a PCR-based screen of kinases), but were ultimately published as "Janus kinase". The name is taken from the two-faced Roman god of beginnings, endings and duality, Janus, because the JAKs possess two near-identical phosphate-transferring domains. One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first. Family The four JAK family members are: * Janus kinase 1 (JAK1) * Janus kinase 2 (JAK2) * Janus kinase 3 (JAK3) * Tyrosine kinase 2 (TYK2) Transgenic mice that do not express JAK1 have defective responses to some cytokines, such as interferon-gamma. JAK1 and JAK2 are involved in type II interferon (interferon-gamma) signalling, whereas JAK1 and TYK2 are involved in type I int ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine Kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions. Tyrosine kinases belong to a larger class of enzymes known as protein kinases which also attach phosphates to other amino acids such as serine and threonine. Phosphorylation of proteins by kinases is an important mechanism for communicating signals within a cell (signal transduction) and regulating cellular activity, such as cell division. Protein kinases can become mutated, stuck in the "on" position, and cause unregulated growth of the cell, which is a necessary step for the development of cancer. Therefore, kinase inhibitors, such as imatinib and osimertinib, are often effective cancer treatments. Most tyrosine kinases have an associated protein tyrosine phosphatase, which removes the phosphate group. Reaction Protein kinases are a group of enzymes that possess a c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interleukin 2
Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15.5–16 kDa protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity. IL-2 is part of the body's natural response to microbial infection, and in discriminating between foreign ("non-self") and "self". IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes. The major sources of IL-2 are activated CD4+ T cells and activated CD8+ T cells. IL-2 receptor IL-2 is a member of a cytokine family, each member of which has a four alpha helix bundle; the family also includes IL-4, IL-7, IL-9, IL-15 and IL-21. IL-2 signals through the IL-2 receptor, a complex consisting of three chains, termed alpha ( CD25), beta ( CD122) and gamma ( CD132). The gamma chain is shared by all family members. The IL-2 receptor (IL-2R) α subunit binds IL-2 with low affinity ( ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interleukin 21
Interleukin 21 (IL-21) is a protein that in humans is encoded by the ''IL21'' gene. Interleukin-21 is a cytokine that has potent regulatory effects on cells of the immune system, including natural killer (NK) cells and cytotoxic T cells that can destroy virally infected or cancerous cells. This cytokine induces cell division/ proliferation in its target cells. Gene The human IL-21 gene is about 8.43kb, mapped to chromosome 4 and 180kb from IL-2 gene, and the mRNA product is 616 nucleotides long. Tissue and cell distribution IL-21 is expressed in activated human CD4+ T cells but not in most other tissues. In addition, IL-21 expression is up-regulated in Th2 and Th17 subsets of T helper cells, as well as T follicular cells. In fact, it was shown that IL-21 can be used to identify peripheral T follicular helper cells. Furthermore, IL-21 is expressed in NK T cells regulating the function of these cells. Interleukin-21 is also produced by Hodgkin's lymphoma (HL) cancer cel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Common Gamma Chain
The common gamma chain (γc) (or CD132), also known as interleukin-2 receptor subunit gamma or IL-2RG, is a cytokine receptor sub-unit that is common to the receptor complexes for at least six different interleukin receptors: IL-2, IL-4, IL-7, IL-9, IL-15 and interleukin-21 receptor. The γc glycoprotein is a member of the type I cytokine receptor family expressed on most lymphocyte (white blood cell) populations, and its gene is found on the X-chromosome of mammals. This protein is located on the surface of immature blood-forming cells in bone marrow. One end of the protein resides outside the cell where it binds to cytokines and the other end of the protein resides in the interior of the cell where it transmits signals to the cell's nucleus. The common gamma chain partners with other proteins to direct blood-forming cells to form lymphocytes (a type of white blood cell). The receptor also directs the growth and maturation of lymphocyte subtypes: T cells, B cells, and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
IFN-a
The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cytoband over approximately 400 kb including coding genes for IFNα (''IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17'' and ''IFNA21''), IFNω (''IFNW1''), IFNɛ (''IFNE''), IFNк (''IFNK'') and IFNβ (''IFNB1''), plus 11 IFN pseudogenes. Interferons bind to interferon receptors. All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains. Type I IFNs are found in all mammals, and homologous (similar) molecules have been found in birds, reptiles, amphibians and fish species. Sources and functions IFN-α and IFN-β are secreted by many cell types including lymphocytes (NK cells, B-cells and T-cells), macrophages, fibr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interleukin 6
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. IL-6's role as an anti-inflammatory myokine is mediated through its inhibitory effects on TNF-alpha and IL-1 and its activation of IL-1ra and IL-10. There is some early evidence that IL-6 can be used as an inflammatory marker for severe COVID-19 infection with poor prognosis, in the context of the wider coronavirus pandemic. Function Immune system IL-6 is secreted by macrophages in response to specific microbial molecules, referred to as pathogen-associated molecular patterns ( PAMPs). These PAMPs bind to an important group of detection molecules of the innate immune system, called pattern recognition receptors (PRRs) ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
IFN-gamma
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed IFN-γ release assay used to test for tuberculosis. In humans, the IFN-γ protein is encoded by the ''IFNG'' gene. Through cell signaling, IFN-γ plays a role in regulating the immune response of its target cell. A key signaling pathway that is activated by type II IFN is the JAK-STAT signal ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. One of these functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins CD8 or ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Interleukin 15
Interleukin-15 (IL-15) is a cytokine with structural similarity to Interleukin-2 (IL-2). Like IL-2, IL-15 binds to and signals through a complex composed of IL-2/IL-15 receptor beta chain ( CD122) and the common gamma chain (gamma-C, CD132). IL-15 is secreted by mononuclear phagocytes (and some other cells) following infection by virus(es). This cytokine induces the proliferation of natural killer cells, i.e. cells of the innate immune system whose principal role is to kill virally infected cells. Expression IL-15 was discovered in 1994 by two different laboratories, and characterized as T cell growth factor. Together with Interleukin-2 ( IL-2), Interleukin-4 ( IL-4), Interleukin-7 ( IL-7), Interleukin-9 ( IL-9), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-15 belongs to the four α-helix bundle family of cytokines. IL-15 is constitutively expressed by a large number of cell types and tissues, inclu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
