|
MTOR
The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases. mTOR links with other proteins and serves as a core component of two distinct protein complexes, mTOR complex 1 and mTOR complex 2, which regulate different cellular processes. In particular, as a core component of both complexes, mTOR functions as a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. As a core component of mTORC2, mTOR also functions as a tyrosine protein kinase that promotes the activation of insulin receptors and insulin-like growth factor 1 receptors. mTORC2 has also been implicated in the control and maintenanc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
MTORC1
mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis. mTOR Complex 1 (mTORC1) is composed of the mammalian target of rapamycin, mTOR protein complex, RPTOR, regulatory-associated protein of mTOR (commonly known as raptor), mammalian lethal with SEC13 protein 8 (MLST8), AKT1S1, PRAS40 and DEPTOR. This complex embodies the classic functions of mTOR, namely as a nutrient/energy/redox sensor and controller of protein synthesis. The activity of this complex is regulated by rapamycin, insulin, growth factors, phosphatidic acid, certain amino acids and their derivatives (e.g., leucine, -leucine and β-hydroxy β-methylbutyric acid), mechanical stimuli, and oxidative stress. Recently it has been also demonstrated that cellular bicarbonate metabolism can be regulated by mTORC1 signaling. The role of mTORC1 is to activate translatio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
MTORC2
mTOR Complex 2 (mTORC2) is an acutely rapamycin-insensitive protein complex formed by serine/threonine kinase mTOR that regulates cell proliferation and survival, cell migration and cytoskeletal remodeling. The complex itself is rather large, consisting of seven protein subunits. The catalytic mTOR subunit, DEP domain containing mTOR-interacting protein ( DEPTOR), mammalian lethal with sec-13 protein 8 ( mLST8, also known as GβL), and TTI1/ TEL2 complex are shared by both mTORC2 and mTORC1. Rapamycin-insensitive companion of mTOR ( RICTOR), mammalian stress-activated protein kinase interacting protein 1 ( mSIN1), and protein observed with rictor 1 and 2 ( Protor1/ 2) can only be found in mTORC2. Rictor has been shown to be the scaffold protein for substrate binding to mTORC2. Function Though less understood than mTORC1, mTORC2 has been shown to respond to growth factors and to modulate cell metabolism and cell survival, thanks to its activation of the survival kinase Ak ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Sirolimus
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumour (PEComa). It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mammalian target of rapamycin (mTOR) kinase inhibitor that reduces the sensitivity of T cells and B cells to interleukin-2 (IL-2), inhibiting their activity. This compound also has a use in cardiovascular drug-eluting stent technologies to inhibit restenosis. It is produced by the bacterium '' Streptomyces hygroscopicus'' and was isolated for the first time in 1972, from samples of ''Streptomyces hygroscopicus'' found on Easter Island. The compound was originally named rapamycin after the native name of the island, Rapa Nui. Sirolimus was initially deve ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Autophagy
Autophagy (or autophagocytosis; from the Greek language, Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. It allows the orderly degradation and recycling of cellular components. Although initially characterized as a primordial degradation pathway induced to protect against starvation, it has become increasingly clear that autophagy also plays a major role in the homeostasis of non-starved cells. Defects in autophagy have been linked to various human diseases, including neurodegeneration and cancer, and interest in modulating autophagy as a potential treatment for these diseases has grown rapidly. Four forms of autophagy have been identified: macroautophagy, microautophagy, chaperone-mediated autophagy (CMA), and crinophagy. In macroautophagy (the most thoroughly researched form of autophagy), cytoplasmic components ( ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Immunosuppressant
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified into five groups: * glucocorticoids * cytostatics * antibodies * drugs acting on immunophilins * other drugs Glucocorticoids In pharmacologic (supraphysiologic) doses, glucocorticoids, such as prednisone, dexamethasone, and hydrocortisone are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. Immunosuppressive mechanism Glucocorticoids suppress cell-mediated immunity. They act by inhibiting gene expression of cytokines including Interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Cell Proliferation
Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation requires both cell growth and cell division to occur at the same time, such that the average size of cells remains constant in the population. Cell division can occur without cell growth, producing many progressively smaller cells (as in cleavage of the zygote), while cell growth can occur without cell division to produce a single larger cell (as in growth of neurons). Thus, cell proliferation is not synonymous with either cell growth or cell division, despite these terms sometimes being used interchangeably. Stem cells undergo cell proliferation to produce proliferating "transit amplifying" daughter cells that later differentiate to construct tissues during normal development and tissue growth, during tissue regeneration after da ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Joseph Heitman
Joseph Heitman is an American physician-scientist focused on research in genetics, microbiology, and infectious diseases. He is the James B. Duke Professor and Chair of the Department of Molecular Genetics and Microbiology at Duke University School of Medicine. Education and career Joseph Heitman grew up in southwestern Michigan and attended Portage Northern High School. He completed a dual Bachelor of Science–Master of Science program in chemistry and biochemistry at the University of Chicago from 1980 to 1984. There he began his research career, working in the laboratories of organic chemist Josef Fried, biochemist Kan Agarwal, and bacteriologist Malcolm Casadaban. In 1984, he began a dual MD–PhD program at Cornell Medical College and Rockefeller University, working on DNA repair in bacteria with Peter Model and Norton Zinder. In 1989, after receiving his PhD from Rockefeller University, Heitman took a leave of absence from medical school to serve as an EMBO-sponsore ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Phosphatidylinositol 3-kinase-related Kinase
Phosphatidylinositol 3-kinase-related kinases (PIKKs) are a family of Ser/Thr-protein kinases with sequence similarity to phosphatidylinositol-3 kinases ( PI3Ks). Members The human PIKK family includes six members: Structure PIKKs proteins contain the following four domains: # N-terminus FRAP-ATM- TRRAP (FAT) domain, # kinase domain (KD; PI3_PI4_kinase), # PIKK- regulatory domain (PRD), and # C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ... FAT-C-terminal (FATC) domain References External links Kinase Family PIKKaWikiKinome EC 2.7.11 Protein families {{protein-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
FK506
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogenic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also be sold as a topical medication in the treatment of T cell-mediated diseases such as eczema and psoriasis. For example, it is prescribed for severe refractory uveitis after a bone marrow transplant, exacerbations of minimal change disease, Kimura's disease, and vitiligo. It can be used to treat dry eye syndrome in cats and dogs. Tacrolimus inhibits calcineurin, which is involved in the production of interleukin-2, a molecule that promotes the development and proliferation of T cells, as part of the body's learned (or adaptive) immune response. Chemically, it is a macrolide lactone that was first discovered in 1987, from the fermentation broth of a Japanese soil sample that contained the bacterium '' Streptomyces tsukubensis''. It is o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
T-lymphocytes
T cells (also known as T lymphocytes) are an important part 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" (cytotoxic) and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins CD8 or CD4.) CD8+ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
Surendra Nath Sehgal
Surendra Nath Sehgal (1932–2003) was an Indian-Canadian-American microbiologist and pharmaceutical scientist most widely known for his discovery and development of ''Rapamycin'' (Sirolimus), a immunosuppressant drug widely used in organ transplantation. Rapamycin has also attracted attention as a potential anti-cancer and anti-aging drug. Early life and education Surendra (Suren) Nath Sehgal, as born in Khushab in pre-partition India (now Pakistan). His father, Sita Ram Sehgal, owned a pharmaceutical factory, but relocated to New Delhi in 1947 after the Partition of India. Sehgal completed a B.Pharm in 1952 and an M.Pharm in 1953 from Banaras Hindu University. At 21, he moved to England to pursue his Ph.D. in Microbiology and Immunology at the University of Bristol, graduating in 1957. Career After completing his Ph.D., Sehgal accepted a postdoctoral fellowship at the National Research Council of Canada. In 1959, he joined Ayerst Research Laboratories in Montreal, becoming ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] [Amazon] |
