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AKT
Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. Family members - Isoforms There are three different genes that encode isoforms of Protein kinase B. These three genes are referred to as AKT1, AKT2, and AKT3 and encode the RAC alpha, beta, and gamma serine/threonine protein kinases respectively. The terms PKB and Akt may refer to the products of all three genes collectively, but sometimes are used to refer to PKB alpha and Akt1 alone. Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes. Akt1 is also able to induce protein synthesis pathways, and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy and general tissue growth. A mouse model with complete deletion of the Akt1 ge ...
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AKT1
RAC(Rho family)-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the ''AKT1'' gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) protein domains. It is commonly referred to as PKB, or by both names as "Akt/PKB". Function The serine-threonine protein kinase AKT1 is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates comp ...
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Akt1
RAC(Rho family)-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the ''AKT1'' gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) protein domains. It is commonly referred to as PKB, or by both names as "Akt/PKB". Function The serine-threonine protein kinase AKT1 is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates comp ...
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PI3K/AKT/mTOR Pathway
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates AKT, localizing it in the plasma membrane. AKT can have a number of downstream effects such as activating CREB, inhibiting p27, localizing FOXO in the cytoplasm, activating PtdIns-3ps, and activating mTOR which can affect transcription of p70 or 4EBP1. There are many known factors that enhance the PI3K/AKT pathway including EGF, shh, IGF-1, insulin, and CaM. Both leptin and insulin recruit PI3K signalling for metabolic regulation. The pathway is antagonized by various factors including PTEN, GSK3B, and HB9. In many cancers, this pathway is overactive, thus reducing apoptosis and allowing proliferation. This pathway is necessary, however, to promote growth and proliferation over differentiation of adult stem cells, neural s ...
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AKT2
AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the ''AKT2'' gene. It influences metabolite storage as part of the insulin signal transduction pathway. Function This gene is a putative oncogene encoding a protein belonging to the AKT subfamily of serine/threonine kinases that contain SH2-like (Src homology 2-like) domains. The encoded protein is a general protein kinase capable of phosphorylating several known proteins. AKT2 has important roles in controlling glycogenesis, gluconeogenesis, and glucose transport as part of the insulin signal transduction pathway. Clinical significance The gene was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers. Mice lacking Akt2 have a normal body mass, but display a profound diabetic phenotype, indicating that A ...
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Akt2
AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the ''AKT2'' gene. It influences metabolite storage as part of the insulin signal transduction pathway. Function This gene is a putative oncogene encoding a protein belonging to the AKT subfamily of serine/threonine kinases that contain SH2-like (Src homology 2-like) domains. The encoded protein is a general protein kinase capable of phosphorylating several known proteins. AKT2 has important roles in controlling glycogenesis, gluconeogenesis, and glucose transport as part of the insulin signal transduction pathway. Clinical significance The gene was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers. Mice lacking Akt2 have a normal body mass, but display a profound diabetic phenotype, indicating that A ...
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AKT3
RAC-gamma serine/threonine-protein kinase is an enzyme that in humans is encoded by the ''AKT3'' gene. Function The protein encoded by this gene is a member of the AKT subfamily of serine/threonine protein kinases. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described. Mice lacking Akt3 have a normal glucose metabolism (no diabetes), have approximately normal body weight, but have a 25% reduction in brain mass. Incidentally, Akt3 is highly expressed in the brain. Interactions AKT3 has been shown to interact with Protein kinase Mζ ...
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Akt3
RAC-gamma serine/threonine-protein kinase is an enzyme that in humans is encoded by the ''AKT3'' gene. Function The protein encoded by this gene is a member of the AKT subfamily of serine/threonine protein kinases. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described. Mice lacking Akt3 have a normal glucose metabolism (no diabetes), have approximately normal body weight, but have a 25% reduction in brain mass. Incidentally, Akt3 is highly expressed in the brain. Interactions AKT3 has been shown to interact with Protein kinase Mζ ...
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Phosphatidylinositol (3,4)-bisphosphate
Phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)''P''2) is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)''P''2 at the plasma membrane activates a number of important cell signaling pathways. Of all the phospholipids found within the membrane, inositol phospholipids make up less than 10%. Phosphoinositide’s (PI’s) also known as phosphatidylinositol phosphates, are synthesized in the cells endoplasmic reticulum by the protein phosphatidylinositol synthase (PIS). PI’s are highly compartmentalized, their main components include a glycerol backbone, two fatty acid chains enriched with stearic acid and arachidonic acid, and an inositol ring whose phosphate groups regulation differs between organelles depending on the specific PI and PIP kinases and PIP phosphatases present in the organelle (Image 1). These kinases and phosphatases conduct phosphorylation and dephosphorylation at the inositol sugar head groups ...
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Phosphoinositide 3-kinase
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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Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apopt ...
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Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apopt ...
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Serine/threonine-specific Protein Kinase
A serine/threonine protein kinase () is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human protein kinases are serine/threonine kinases (STK). In enzymology, the term ''serine/threonine protein kinase'' describes a class of enzymes in the family of transferases, that transfer phosphates to the oxygen atom of a serine or threonine side chain in proteins. This process is called phosphorylation. Protein phosphorylation in particular plays a significant role in a wide range of cellular processes and is a very important posttranslational modification. The chemical reaction performed by these enzymes can be written as :ATP + a protein \rightleftharpoons ADP + a phosphoprotein Thus, the two substrates of this enzyme are ATP and a protein, whereas its two products are ADP and phosphoprotein. The systematic name of this enzyme clas ...
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