Lck
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Lck
Lck (or lymphocyte-specific protein tyrosine kinase) is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. The Lck is a member of Src kinase family (SFK), it is important for the activation of the T-cell receptor signaling in both naive T cells and effector T cells. The role of the Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the role of the lck varies among the memory T cells subsets. It seems that in mice, in the effector memory T cells (TEM) population, more than 50% of lck is present in a constitutively active conformation, whereas, only less than 20% of lck is present as active form of lck. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase. The Lck is responsible for the initiation of the TCR signaling cascade inside the cell by phosphorylating immunoreceptor tyrosine†...
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ZAP-70
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 ...
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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 ...
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Lipid Raft
The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. It has been proposed that they are specialized membrane microdomains which compartmentalize cellular processes by serving as organising centers for the assembly of signaling molecules, allowing a closer interaction of protein receptors and their effectors to promote kinetically favorable interactions necessary for the signal transduction. Lipid rafts influence membrane fluidity and membrane protein trafficking, thereby regulating neurotransmission and receptor trafficking. Lipid rafts are more ordered and tightly packed than the surrounding bilayer, but float freely within the membrane bilayer. Although more common in the cell membrane, lipid rafts have also been reported in other parts of the cell, such as the Golgi apparatus and lysosome ...
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Cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as ''Helicobacter pylori'', hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes of ...
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Atomic Mass Unit
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. The atomic mass constant, denoted ''m''u, is defined identically, giving . This unit is commonly used in physics and chemistry to express the mass of atomic-scale objects, such as atoms, molecules, and elementary particles, both for discrete instances and multiple types of ensemble averages. For example, an atom of helium-4 has a mass of . This is an intrinsic property of the isotope and all helium-4 atoms have the same mass. Acetylsalicylic acid (aspirin), , has an average mass of approximately . However, there are no acetylsalicylic acid molecules with this mass. The two most common masses of individual acetylsalicylic acid molecules are , having the most common isotopes, and , in which one carbon is carbon-13. The molecular mass ...
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Thymus
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. The thymus is located in the upper front part of the chest, in the anterior superior mediastinum, behind the sternum, and in front of the heart. It is made up of two lobes, each consisting of a central medulla and an outer cortex, surrounded by a capsule. The thymus is made up of immature T cells called thymocytes, as well as lining cells called epithelial cells which help the thymocytes develop. T cells that successfully develop react appropriately with MHC immune receptors of the body (called ''positive selection'') and not against proteins of the body (called ''negative selection''). The thymus is largest and most active during the neonatal and pre-adolescent periods. By the early teens, the thymus begins to decrease in size and a ...
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PI3K
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. PI3Ks are a family of related intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). The pathway, with oncogene PIK3CA and tumor suppressor gene PTEN, is implicated in the sensitivity of cancer tumors to insulin and IGF1, and in calorie restriction. Discovery The discovery of PI3Ks by Lewis Cantley and colleagues began with their identification of a previously unknown phosphoinositide kinase associated with the polyoma middle T protein. They observed unique substrate specificity and chromatographic properties of the products of the lipid kinase, leading to the discovery that this phosphoinositide kinase had ...
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Transmembrane Protein
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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Linker For Activation Of T Cells
The Linker for activation of T cells, also known as linker of activated T cells or LAT, is a protein involved in the T-cell antigen receptor signal transduction pathway which in humans is encoded by the ''LAT'' gene. Alternative splicing results in multiple transcript variants encoding different isoforms. Function The LAT protein encoded by the gene of the same name, plays a key role in the diversification of T cell signaling pathways following activation of the T-cell antigen receptor ( TCR) signal transduction pathway, which is first catalyzed by TCR binding to MHC class II. LAT is a transmembrane protein localizes to lipid rafts (also known as glycosphingolipid-enriched microdomains or GEMs) and acts as a docking site for SH2 domain-containing proteins. Upon phosphorylation, this protein recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement. In mouse thymocytes, lack of functiona ...
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Kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule donates a phosphate group to the substrate molecule. This transesterification produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group (producing a dephosphorylated substrate and the high energy molecule of ATP). These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis. Kinases are part of the larger family of phosphotransferases. Kinases should not be confused with phosphorylases, which catalyze the addition of inorganic phosphate groups to an acceptor, nor with phosphatases, which remove phosphate groups (dephosphorylation). The phosphorylation state of a molecule, whet ...
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Tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Greek ''tyrĂłs'', meaning ''cheese'', as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. It is called tyrosyl when referred to as a functional group or side chain. While tyrosine is generally classified as a Hydrophobe, hydrophobic amino acid, it is more hydrophilic than phenylalanine. It is Genetic code, encoded by the Genetic code#Codons, codons UAC and UAU in messenger RNA. Functions Aside from being a proteinogenic amino acid, tyrosine has a special role by virtue of the phenol functionality. It occurs in proteins that are part of signal transduction processes and functions as a receiver of phosphate groups that are transferred by way of protein kinases. Phosphorylation of the hyd ...
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