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Syk
Tyrosine-protein kinase SYK, also known as spleen tyrosine kinase, is an enzyme which in humans is encoded by the ''SYK'' gene. Function SYK, along with ZAP70, is a member of the Syk family of tyrosine kinases. These cytoplasmic non-receptor tyrosine kinases share a characteristic dual SH2 domain separated by a linker domain. However, activation of SYK relies less on phosphorylation by Src family kinases than ZAP70. SYK and ZAP70 share a common evolutionary origin and split from a common ancestor in the jawed vertebrates. While Syk and ZAP70 are primarily expressed in hematopoietic tissues, a variety tissues express Syk. Within B and T cells, respectively, Syk and ZAP70 transmit signals from the B-cell receptor and T-cell receptor. Syk plays a similar role in transmitting signals from a variety of cell surface receptors including CD74, Fc receptor, and integrins. Function during development Mice that lack Syk completely (Syk−/−, Syk-knockout) die during embryonic dev ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Non-receptor Tyrosine Kinase
A non-receptor tyrosine kinase (nRTK) is a cytosolic enzyme that is responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell. Unlike the receptor tyrosine kinases (RTKs), the second subgroup of tyrosine kinases, the non-receptor tyrosine kinases are cytosolic enzymes. Thirty-two non-receptor tyrosine kinases have been identified in human cells (). Non-receptor tyrosine kinases regulate cell growth, proliferation, differentiation, adhesion, migration and apoptosis, and they are critical components in the regulation of the immune system. Function The main function of nRTKs is their involvement in sign ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ZAP70
ZAP-70 (Zeta-chain-associated protein kinase 70) is a protein normally expressed near the surface membrane of lymphocytes (T cells, natural killer cells, and a subset of B cells). It is most prominently known to be recruited upon antigen binding to the T cell receptor (TCR), and it plays a critical role in T cell signaling. ZAP-70 was initially discovered in TCR-stimulated Jurkat cells, an immortal line of human T lymphocytes, in 1991. Its molecular weight is 70 kDa, and it is a member of the protein-tyrosine kinase family and is a close homolog of SYK. SYK and ZAP70 share a common evolutionary origin and split from a common ancestor in the jawed vertebrates. The importance of ZAP-70 in T cell activation was determined when comparing ZAP-70 expression in patients with SCID (severe combined immunodeficiency). ZAP-70 deficient individuals were found to have no functioning T cells in their peripheral blood, suggesting that ZAP-70 is a critical component of T cell activation and de ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fostamatinib
Fostamatinib, sold under the brand names Tavalisse and Tavlesse, is a tyrosine kinase inhibitor medication for the treatment of chronic immune thrombocytopenia (ITP). The drug is administered by mouth. Fostamatinib blocks the activity of the enzyme spleen tyrosine kinase (SYK). This enzyme is involved in stimulating parts of the immune system. By blocking SYK's activity, fostamatinib reduces the immune system's destruction of platelets, so allowing the platelet count to rise, which reduces the likelihood of excessive bleeding. The most commonly reported side effects are diarrhea, high blood pressure, nausea, respiratory infection, dizziness, increased liver enzymes, rash, abdominal pain, fatigue, chest pain and decreased white blood cell count. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses Fostamatinib is a drug used to treat adults with low platelet count due to chronic immune thrombocytopenia (ITP) when a prior tr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunoreceptor Tyrosine-based Activation Motif
An immunoreceptor tyrosine-based activation motif (ITAM) is a conserved sequence of four amino acids that is repeated twice in the cytoplasmic tails of non-catalytic tyrosine-phosphorylated receptors, cell-surface proteins found mainly on immune cells. Its major role is being an integral component for the initiation of a variety of signaling pathway and subsequently the activation of immune cells, although different functions have been described, for example an osteoclast maturation. Structure The motif contains a tyrosine separated from a leucine or isoleucine by any two other amino acids, giving the signature YxxL/I. Two of these signatures are typically separated by between 6 and 8 amino acids in the cytoplasmic tail of the molecule (YxxL/Ix(6-8)YxxL/I). However, it is worth noting that in various sources, this consensus sequence differs, mainly in the number of amino acids between individual signatures. Apart from ITAMs which have the structure described above, there is als ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
B-cell Receptor
The B cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, and is typically located on the outer surface of these lymphocyte cells. Through biochemical signaling and by physically acquiring antigens from the immune synapses, the BCR controls the activation of the B cell. B cells are able to gather and grab antigens by engaging biochemical modules for receptor clustering, cell spreading, generation of pulling forces, and receptor transport, which eventually culminates in endocytosis and antigen presentation. B cells' mechanical activity adheres to a pattern of negative and positive feedbacks that regulate the quantity of removed antigen by manipulating the dynamic of BCR–antigen bonds directly. Particularly, grouping and spreading increase the relation of antigen with BCR, thereby proving sensit ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cerdulatinib
Cerdulatinib is a small molecule SYK/JAK kinase inhibitor in development for treatment of hematological malignancies. It has lowest nM IC50 values against TYK2, JAK1, JAK2, JAK3, FMS, and SYK. It is being developed by Portola Pharmaceuticals; in September 2018 the FDA granted orphan drug status to cerdulatinib for the treatment of peripheral T-cell lymphoma (PTCL).{{Cite web, url=http://phx.corporate-ir.net/phoenix.zhtml?c=198136&p=irol-newsArticle&ID=2368929, title=Investors - News Release - Portola Pharmaceuticals, Inc., website=phx.corporate-ir.net, language=en, date=September 25, 2018 See also * Ruxolitinib * Fostamatinib * Entospletinib Entospletinib is an experimental drug for the treatment of various types of cancer under development by Gilead Sciences. It is an inhibitor of spleen tyrosine kinase (Syk). It has entered clinical trials for acute myeloid leukaemia (AML), chro ... References Experimental cancer drugs Protein kinase inhibitors Aminopyri ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, night sweats, or weight loss for no clear reason may occur. Enlargement of the spleen and low red blood cells (anemia) may also occur. It typically worsens gradually over years. Risk factors include having a family history of the disease, with 10% of those who develop CLL having a family history of the disease. Exposure to Agent Orange, certain insecticides, sun exposure, exposure to hepatitis C virus, and common infections are also considered risk factors. CLL results in the buildup of B cell lymphocytes in the bone marrow, lymph nodes, and blood. These cells do not function well and crowd out healthy blood cells. CLL is divided into two main types: those with a mutated IGHV gene and those without. Diagnosis is typically based o ... [...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] |
SH2 Domain
The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosphorylated tyrosine residues on other proteins. SH2 domains are commonly found in adaptor proteins that aid in the signal transduction of receptor tyrosine kinase pathways. Background SH2 is conserved by signalization of protein tyrosine kinase, which are binding on phosphotyrosine (pTyr). In the human proteome the class of pTyr-selective recognition domains is represented by SH2 domains. The N-terminal SH2 domains of cytoplasmic tyrosine kinase was at the beginning of evolution evolved with the occurrence of tyrosine phosphorylation. At the beginning it was supposed that, these domains serve as a substrate for their target kinase. Protein-protein interactions play a major role in cellular growth and development. Modular domains, which are t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Entospletinib
Entospletinib is an experimental drug for the treatment of various types of cancer under development by Gilead Sciences. It is an inhibitor of spleen tyrosine kinase (Syk). It has entered clinical trials for acute myeloid leukaemia (AML), chronic lymphocytic leukemia (CLL), diffuse large B cell lymphoma (DLBCL), graft-versus-host disease (GvHD), hematological malignancies, mantle cell lymphoma (MCL), and non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredne ... (NHL). References Experimental cancer drugs Tyrosine kinase inhibitors 4-Morpholinyl compunds Indazoles {{antineoplastic-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the react ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mouse Mammary Tumor Virus
Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus like the HTL viruses, HI viruses, and BLV. It belongs to the genus ''Betaretrovirus''. MMTV was formerly known as Bittner virus, and previously the "milk factor", referring to the extra-chromosomal vertical transmission of murine breast cancer by adoptive nursing, demonstrated in 1936, by John Joseph Bittner while working at the Jackson Laboratory in Bar Harbor, Maine. Bittner established the theory that a cancerous agent, or "milk factor", could be transmitted by cancerous mothers to young mice from a virus in their mother's milk. The majority of mammary tumors in mice are caused by mouse mammary tumor virus. Infection and life cycle Several mouse strains carry the virus endogenously, but it is also transmitted vertically via milk from mother to pup. It is contained as a DNA provirus integrated in the DNA of milk lymphocytes. The viruses become transported through the gastrointestinal tract to the Peyer's pat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
