A subclass of phosphatidylinositol 3-kinases that have specificity for 1-phosphatidylinositol and 1-phosphatidylinositol 4-phosphate. Members of this subclass consist of a single subunit structure and are regulated by RECEPTOR TYROSINE KINASES; CYTOKINE RECEPTORS; and INTEGRINS.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.
A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Genetic loci in the vertebrate major histocompatibility complex that encode polymorphic products which control the immune response to specific antigens. The genes are found in the HLA-D region in humans and in the I region in mice.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Chromones are a class of chemical compounds that contain a benzopyran-4-one core structure, which are found in various natural and synthetic substances, including some medications used to treat asthma and allergies.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Morpholines are organic compounds containing a morpholine ring, which is a saturated six-membered heterocycle made up of four carbon atoms and two oxygen atoms (OCC1CCO), often used as functional groups in pharmaceuticals, agrochemicals, and materials science due to their versatile chemical properties.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Agents that inhibit PROTEIN KINASES.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Established cell cultures that have the potential to propagate indefinitely.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

Mitotic and stress-induced phosphorylation of HsPI3K-C2alpha targets the protein for degradation. (1/22)

Activation of the phosphoinositide 3-kinases (PI 3-kinases) has been implicated in multiple cellular responses such as proliferation and survival, membrane and cytoskeletal reorganization, and intracellular vesicular trafficking. The activities and subcellular localization of PI 3-kinases were shown to be regulated by phosphorylation. Previously we demonstrated that class II HsPIK3-C2alpha becomes phosphorylated upon inhibition of RNA pol II-dependent transcription (Didichenko, S. A., and Thelen, M. (2001) J. Biol. Chem. 276, 48135-48142). In this study we investigated cell cycle-dependent and genotoxic stress-induced phosphorylation of HsPIK3-C2alpha. We find that the kinase becomes phosphorylated upon exposure of cells to UV irradiation and in proliferating cells at the G2/M transition of the cell cycle. Stress-dependent and mitotic phosphorylation of HsPIK3-C2alpha occurs on the same serine residue (Ser259) within a recognition motif for proline-directed kinases. Mitotic phosphorylation of HsPIK3-C2alpha can be attributed to Cdc2 activity, and stress-induced phosphorylation of HsPIK3-C2alpha is mediated by JNK/SAPK. The protein level of HsPIK3-C2alpha is regulated by proteolysis in a cell cycle-dependent manner and in response of cells to stress. Phosphorylation appears to be a prerequisite for proteasome-dependent degradation of HsPIK3-C2alpha and may therefore contribute indirectly to the regulation of the activity of the kinase.  (+info)

Phosphatidylinositol 3-kinase C2alpha is essential for ATP-dependent priming of neurosecretory granule exocytosis. (2/22)

Neurotransmitter release and hormonal secretion are highly regulated processes culminating in the calcium-dependent fusion of secretory vesicles with the plasma membrane. Here, we have identified a role for phosphatidylinositol 3-kinase C2alpha (PI3K-C2alpha) and its main catalytic product, PtdIns3P, in regulated exocytosis. In neuroendocrine cells, PI3K-C2alpha is present on a subpopulation of mature secretory granules. Impairment of PI3K-C2alpha function specifically inhibits the ATP-dependent priming phase of exocytosis. Overexpression of wild-type PI3K-C2alpha enhanced secretion, whereas transfection of PC12 cells with a catalytically inactive PI3K-C2alpha mutant or a 2xFYVE domain sequestering PtdIns3P abolished secretion. Based on these results, we propose that production of PtdIns3P by PI3K-C2alpha is required for acquisition of fusion competence in neurosecretion.  (+info)

Individual phosphoinositide 3-kinase C2alpha domain activities independently regulate clathrin function. (3/22)

Phosphoinositide 3-kinase C2alpha (PI3K-C2alpha) is a member of the class II PI-3 kinases, defined by the presence of a second C2 domain at their C termini. The cellular functions of the class II enzymes are incompletely understood, though they have been implicated in receptor activation pathways initiated by epidermal growth factor, insulin, and chemokines. PI3K-C2alpha was recently found to be localized to clathrin-coated membranes in the trans-Golgi network and at endocytic sites on the plasma membrane. Further, a specific binding site was identified for clathrin on the N terminus of PI3K-C2alpha, whose occupancy resulted in lipid kinase activation. Expression of PI3K-C2alpha in cells dramatically affected clathrin distribution and function in cells, leading to accumulation of intracellular clathrin-coated structures, which are visualized here at the ultrastructural level, and inhibition of clathrin-mediated transport from both the plasma membrane and the trans-Golgi network. In this study we have demonstrated that the isolated clathrin binding domain of PI3K-C2alpha can drive clathrin lattice assembly and that both it and the lipid kinase activity of the protein can independently modulate clathrin distribution and function when expressed in cells. Together, these results suggest that PI3K-C2alpha employs both protein-protein interaction and localized production of 3-phosphoinositides to affect clathrin dynamics at sites of membrane budding and targeting.  (+info)

The class II phosphoinositide 3-kinase C2beta is not essential for epidermal differentiation. (4/22)

Phosphoinositide 3-kinases (PI3Ks) regulate an array of cellular processes and are comprised of three classes. Class I PI3Ks include the well-studied agonist-sensitive p110 isoforms; however, the functions of class II and III PI3Ks are less well characterized. Of the three class II PI3Ks, C2alpha and C2beta are widely expressed in many tissues, including the epidermis, while C2gamma is confined to the liver. In contrast to the class I PI3K p110alpha, which is expressed throughout the epidermis, C2beta was found to be localized in suprabasal cells, suggesting a potential role for C2beta in epidermal differentiation. Overexpressing C2beta in epidermal cells in vitro induced differentiation markers. To study a role for C2beta in tissue, we generated transgenic mice overexpressing C2beta in both suprabasal and basal epidermal layers. These mice lacked epidermal abnormalities. Mice deficient in C2beta were then generated by targeted gene deletion. C2beta knockout mice were viable and fertile and displayed normal epidermal growth, differentiation, barrier function, and wound healing. To exclude compensation by C2alpha, RNA interference was then used to knock down both C2alpha and C2beta in epidermal cells simultaneously. Induction of differentiation markers was unaffected in the absence of C2alpha and C2beta. These findings indicate that class II PI3Ks are not essential for epidermal differentiation.  (+info)

Class II phosphoinositide 3-kinase alpha-isoform regulates Rho, myosin phosphatase and contraction in vascular smooth muscle. (5/22)

We demonstrated previously that membrane depolarization and excitatory receptor agonists such as noradrenaline induce Ca2+-dependent Rho activation in VSM (vascular smooth muscle), resulting in MP (myosin phosphatase) inhibition through the mechanisms involving Rho kinase-mediated phosphorylation of its regulatory subunit MYPT1. In the present study, we show in de-endothelialized VSM strips that the PI3K (phosphoinositide 3-kinase) inhibitors LY294002 and wortmannin inhibited KCl membrane depolarization- and noradrenaline-induced Rho activation and MYPT1 phosphorylation, with concomitant inhibition of MLC (20-kDa myosin light chain) phosphorylation and contraction. LY294002 also augmented de-phosphorylation of MLC and resultantly relaxation in KCl-contracted VSM, whereas LY294002 was much less effective or ineffective under the conditions in which MP was inhibited by either a phosphatase inhibitor or a phorbol ester in Rho-independent manners. VSM express at least four PI3K isoforms, including the class I enzymes p110alpha and p110beta and the class II enzymes PI3K-C2alpha and -C2beta. The dose-response relationships of PI3K-inhibitor-induced inhibition of Rho, MLC phosphorylation and contraction were similar to that of PI3K-C2alpha inhibition, but not to that of the class I PI3K inhibition. Moreover, KCl and noradrenaline induced stimulation of PI3K-C2alpha in a Ca2+-dependent manner, but not of p110alpha or p110beta. Down-regulation of PI3K-C2alpha expression by siRNA (small interfering RNA) inhibited contraction and phosphorylation of MYPT1 and MLC in VSM cells. Finally, intravenous wortmannin infusion induced sustained hypotension in rats, with inhibition of PI3K-C2alpha activity, GTP-loading of Rho and MYPT1 phosphorylation in the artery. These results indicate the novel role of PI3K-C2alpha in Ca2+-dependent Rho-mediated negative control of MP and thus VSM contraction.  (+info)

Structural and membrane binding analysis of the Phox homology domain of phosphoinositide 3-kinase-C2alpha. (6/22)

Phox homology (PX) domains, which have been identified in a variety of proteins involved in cell signaling and membrane trafficking, have been shown to interact with phosphoinositides (PIs) with different affinities and specificities. To elucidate the structural origin of diverse PI specificities of PX domains, we determined the crystal structure of the PX domain from phosphoinositide 3-kinase C2alpha (PI3K-C2alpha), which binds phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). To delineate the mechanism by which this PX domain interacts with membranes, we measured the membrane binding of the wild type domain and mutants by surface plasmon resonance and monolayer techniques. This PX domain contains a signature PI-binding site that is optimized for PtdIns(4,5)P(2) binding. The membrane binding of the PX domain is initiated by nonspecific electrostatic interactions followed by the membrane penetration of hydrophobic residues. Membrane penetration is specifically enhanced by PtdIns(4,5)P(2). Furthermore, the PX domain displayed significantly higher PtdIns(4,5)P(2) membrane affinity and specificity when compared with the PI3K-C2alpha C2 domain, demonstrating that high affinity PtdIns(4,5)P(2) binding was facilitated by the PX domain in full-length PI3K-C2alpha. Together, these studies provide new structural insight into the diverse PI specificities of PX domains and elucidate the mechanism by which the PI3K-C2alpha PX domain interacts with PtdIns(4,5)P(2)-containing membranes and thereby mediates the membrane recruitment of PI3K-C2alpha.  (+info)

Phosphoinositide 3-kinase C2alpha links clathrin to microtubule-dependent movement. (7/22)

Phosphoinositide 3-kinase C2alpha (PI3K-C2alpha) is a type II PI-3-kinase that has been implicated in several important membrane transport and signaling processes. We previously found that overexpression of PI3K-C2alpha inhibits clathrin-mediated membrane trafficking and induces proliferation of novel clathrin-coated structures within the cytoplasm. Using fluorescently tagged fusions of PI3K-C2alpha and clathrin, we explored the behavior of these structures in intact cells. Both proteins are present in the structures, and using rapid image acquisition and fluorescence photoactivation probes, we find that they exhibit localized, rapid mobility (5-20 microm/s). The movement is micro-tubule-based as revealed by use of inhibitors, and PI3K-C2alpha accumulates on microtubules rapidly and reversibly following cytoplasmic acidification, which also blocks movement. Dynactin mediates the movement of these clathrin-PI3K-C2alpha structures, since disruption of dynactin function by overexpression of its p50 subunit also inhibits movement. Finally, immunoprecipitation experiments reveal an interaction between endogenous PI3K-C2alpha and dynactin subunits. Together, these results reveal a molecular linkage between PI3K-C2alpha and the microtubule motor machinery, with implications for membrane trafficking in intact cells.  (+info)

Ca2+-independent, inhibitory effects of cyclic adenosine 5'-monophosphate on Ca2+ regulation of phosphoinositide 3-kinase C2alpha, Rho, and myosin phosphatase in vascular smooth muscle. (8/22)

We have recently demonstrated in vascular smooth muscle (VSM) that membrane depolarization by high KCl induces Ca(2+)-dependent Rho activation and myosin phosphatase (MLCP) inhibition (Ca(2+)-induced Ca(2+)-sensitization) through the mechanisms involving phosphorylation of myosin-targeting protein 1 (MYPT1) and 17-kDa protein kinase C (PKC)-potentiated inhibitory protein of PP1 (CPI-17). In the present study, we investigated whether and how cAMP affected Ca(2+)-dependent MLCP inhibition by examining the effects of forskolin, cell-permeable dibutyryl cAMP (dbcAMP), and isoproterenol. Forskolin, but not its inactive analog 1,9-dideoxyforskolin, inhibited KCl-induced contraction and the 20-kDa myosin light chain (MLC) phosphorylation without inhibiting Ca(2+) mobilization in rabbit aortic VSM. dbcAMP mimicked these forskolin effects. We recently suggested that Ca(2+)-mediated Rho activation is dependent on class II alpha-isoform of phosphoinositide 3-kinase (PI3K-C2alpha). Forskolin inhibited KCl-induced stimulation of PI3K-C2alpha activity. KCl-induced membrane depolarization stimulated Rho in a manner dependent on a PI3K but not PKC and stimulated phosphorylation of MYPT1 at Thr(850) and CPI-17 at Thr(38) in manners dependent on both PI3K and Rho kinase, but not PKC. Forskolin, dbcAMP, and isoproterenol inhibited KCl-induced Rho activation and phosphorylation of MYPT1 and CPI-17. Consistent with these data, forskolin, isoproterenol, a PI3K inhibitor, or a Rho kinase inhibitor, but not a PKC inhibitor, abolished KCl-induced diphosphorylation of MLC. These observations indicate that cAMP inhibits Ca(2+)-mediated activation of the MLCP-regulating signaling pathway comprising PI3K-C2alpha, Rho, and Rho kinase in a manner independent of Ca(2+) and point to the novel mechanism of the cAMP actions in the regulation of vascular smooth muscle contraction.  (+info)

Class II phosphatidylinositol 3-kinases (PI3Ks) are a subfamily of lipid kinases that specifically phosphorylate the 3-hydroxyl group of the inositol ring in phosphatidylinositol (PI), creating PI 3-phosphate (PI(3)P). These enzymes play crucial roles in various cellular processes, including membrane trafficking, autophagy, and metabolism. Unlike Class I PI3Ks, which are activated by receptor tyrosine kinases and G protein-coupled receptors, Class II PI3Ks are primarily regulated by intracellular signals and interact with various proteins involved in membrane dynamics. There are three isoforms of Class II PI3Ks: PI3K-C2α, PI3K-C2β, and PI3K-C2γ, encoded by the genes PIP5K1A, PIP5K1B, and PIP5K2B, respectively. These isoforms exhibit distinct subcellular localization patterns and substrate preferences, contributing to their unique functions in cell signaling and regulation.

1-Phosphatidylinositol 4-Kinase (PI4K) is a type of enzyme that belongs to the family of kinases, which are enzymes that transfer phosphate groups from high-energy donor molecules to specific target proteins or lipids in the cell. PI4K specifically phosphorylates the 4th position on the inositol ring of phosphatidylinositol (PI), a type of phospholipid found in the cell membrane, converting it to phosphatidylinositol 4-phosphate (PI4P).

PI4K has several isoforms, including PI4K alpha, beta, gamma, and delta, which are located in different cellular compartments and play distinct roles. For example, PI4K alpha and beta are primarily involved in vesicle trafficking and Golgi function, while PI4K gamma and delta are associated with the plasma membrane and regulate ion channels and other signaling pathways.

PI4P, the product of PI4K activity, is an important signaling molecule that regulates various cellular processes, including membrane trafficking, cytoskeleton organization, and protein sorting. Dysregulation of PI4K and its downstream pathways has been implicated in several human diseases, such as cancer, neurodegeneration, and viral infection.

Phosphatidylinositol 3-Kinases (PI3Ks) are a family of enzymes that play a crucial role in intracellular signal transduction. They phosphorylate the 3-hydroxyl group of the inositol ring in phosphatidylinositol and its derivatives, which results in the production of second messengers that regulate various cellular processes such as cell growth, proliferation, differentiation, motility, and survival.

PI3Ks are divided into three classes based on their structure and substrate specificity. Class I PI3Ks are further subdivided into two categories: class IA and class IB. Class IA PI3Ks are heterodimers consisting of a catalytic subunit (p110α, p110β, or p110δ) and a regulatory subunit (p85α, p85β, p55γ, or p50γ). They are primarily activated by receptor tyrosine kinases and G protein-coupled receptors. Class IB PI3Ks consist of a catalytic subunit (p110γ) and a regulatory subunit (p101 or p84/87). They are mainly activated by G protein-coupled receptors.

Dysregulation of PI3K signaling has been implicated in various human diseases, including cancer, diabetes, and autoimmune disorders. Therefore, PI3Ks have emerged as important targets for drug development in these areas.

Phosphatidylinositol phosphates (PIPs) are a family of lipid molecules that play crucial roles as secondary messengers in intracellular signaling pathways. They are formed by the phosphorylation of the hydroxyl group on the inositol ring of phosphatidylinositol (PI), a fundamental component of cell membranes.

There are seven main types of PIPs, classified based on the number and position of phosphate groups attached to the inositol ring:

1. Phosphatidylinositol 4-monophosphate (PI4P) - one phosphate group at the 4th position
2. Phosphatidylinositol 5-monophosphate (PI5P) - one phosphate group at the 5th position
3. Phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) - two phosphate groups at the 3rd and 4th positions
4. Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) - two phosphate groups at the 3rd and 5th positions
5. Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] - two phosphate groups at the 4th and 5th positions
6. Phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] - three phosphate groups at the 3rd, 4th, and 5th positions
7. Phosphatidylinositol 3-phosphate (PI3P) - one phosphate group at the 3rd position

These PIPs are involved in various cellular processes such as membrane trafficking, cytoskeleton organization, cell survival, and metabolism. Dysregulation of PIP metabolism has been implicated in several diseases, including cancer, diabetes, and neurological disorders.

Phosphatidylinositol 4,5-Diphosphate (PIP2) is a phospholipid molecule that plays a crucial role as a secondary messenger in various cell signaling pathways. It is a constituent of the inner leaflet of the plasma membrane and is formed by the phosphorylation of Phosphatidylinositol 4-Phosphate (PIP) at the 5th position of the inositol ring by enzyme Phosphoinositide kinase.

PIP2 is involved in several cellular processes, including regulation of ion channels, cytoskeleton dynamics, and membrane trafficking. It also acts as a substrate for the generation of two important secondary messengers, Inositol 1,4,5-Trisphosphate (IP3) and Diacylglycerol (DAG), which are produced by the action of Phospholipase C enzyme in response to various extracellular signals. These second messengers then mediate a variety of cellular responses such as calcium mobilization, gene expression, and cell proliferation.

Histocompatibility antigens Class II are a group of cell surface proteins that play a crucial role in the immune system's response to foreign substances. They are expressed on the surface of various cells, including immune cells such as B lymphocytes, macrophages, dendritic cells, and activated T lymphocytes.

Class II histocompatibility antigens are encoded by the major histocompatibility complex (MHC) class II genes, which are located on chromosome 6 in humans. These antigens are composed of two non-covalently associated polypeptide chains, an alpha (α) and a beta (β) chain, which form a heterodimer. There are three main types of Class II histocompatibility antigens, known as HLA-DP, HLA-DQ, and HLA-DR.

Class II histocompatibility antigens present peptide antigens to CD4+ T helper cells, which then activate other immune cells, such as B cells and macrophages, to mount an immune response against the presented antigen. Because of their role in initiating an immune response, Class II histocompatibility antigens are important in transplantation medicine, where mismatches between donor and recipient can lead to rejection of the transplanted organ or tissue.

Phosphatidylinositols (PIs) are a type of phospholipid that are abundant in the cell membrane. They contain a glycerol backbone, two fatty acid chains, and a head group consisting of myo-inositol, a cyclic sugar molecule, linked to a phosphate group.

Phosphatidylinositols can be phosphorylated at one or more of the hydroxyl groups on the inositol ring, forming various phosphoinositides (PtdInsPs) with different functions. These signaling molecules play crucial roles in regulating cellular processes such as membrane trafficking, cytoskeletal organization, and signal transduction pathways that control cell growth, differentiation, and survival.

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a prominent phosphoinositide involved in the regulation of ion channels, enzymes, and cytoskeletal proteins. Upon activation of certain receptors, PIP2 can be cleaved by the enzyme phospholipase C into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (InsP3), which act as second messengers to trigger downstream signaling events.

Protein-Serine-Threonine Kinases (PSTKs) are a type of protein kinase that catalyzes the transfer of a phosphate group from ATP to the hydroxyl side chains of serine or threonine residues on target proteins. This phosphorylation process plays a crucial role in various cellular signaling pathways, including regulation of metabolism, gene expression, cell cycle progression, and apoptosis. PSTKs are involved in many physiological and pathological processes, and their dysregulation has been implicated in several diseases, such as cancer, diabetes, and neurodegenerative disorders.

Major Histocompatibility Complex (MHC) Class II genes are a group of genes that encode cell surface proteins responsible for presenting peptide antigens to CD4+ T cells, which are crucial in the adaptive immune response. These proteins are expressed mainly on professional antigen-presenting cells such as dendritic cells, macrophages, and B cells. MHC Class II molecules present extracellular antigens derived from bacteria, viruses, and other pathogens, facilitating the activation of appropriate immune responses to eliminate the threat. The genes responsible for these proteins are found within the MHC locus on chromosome 6 in humans (chromosome 17 in mice).

Mitogen-activated protein kinase (MAPK) signaling system is a crucial pathway for the transmission and regulation of various cellular responses in eukaryotic cells. It plays a significant role in several biological processes, including proliferation, differentiation, apoptosis, inflammation, and stress response. The MAPK cascade consists of three main components: MAP kinase kinase kinase (MAP3K or MEKK), MAP kinase kinase (MAP2K or MEK), and MAP kinase (MAPK).

The signaling system is activated by various extracellular stimuli, such as growth factors, cytokines, hormones, and stress signals. These stimuli initiate a phosphorylation cascade that ultimately leads to the activation of MAPKs. The activated MAPKs then translocate into the nucleus and regulate gene expression by phosphorylating various transcription factors and other regulatory proteins.

There are four major MAPK families: extracellular signal-regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK1/2/3), p38 MAPKs (p38α/β/γ/δ), and ERK5. Each family has distinct functions, substrates, and upstream activators. Dysregulation of the MAPK signaling system can lead to various diseases, including cancer, diabetes, cardiovascular diseases, and neurological disorders. Therefore, understanding the molecular mechanisms underlying this pathway is crucial for developing novel therapeutic strategies.

Chromones are a type of chemical compound that contain a benzopyran ring, which is a structural component made up of a benzene ring fused to a pyran ring. They can be found in various plants and have been used in medicine for their anti-inflammatory, antimicrobial, and antitussive (cough suppressant) properties. Some chromones are also known to have estrogenic activity and have been studied for their potential use in hormone replacement therapy. Additionally, some synthetic chromones have been developed as drugs for the treatment of asthma and other respiratory disorders.

Androstadienes are a class of steroid hormones that are derived from androstenedione, which is a weak male sex hormone. Androstadienes include various compounds such as androstadiene-3,17-dione and androstanedione, which are intermediate products in the biosynthesis of more potent androgens like testosterone and dihydrotestosterone.

Androstadienes are present in both males and females but are found in higher concentrations in men. They can be detected in various bodily fluids, including blood, urine, sweat, and semen. In addition to their role in steroid hormone synthesis, androstadienes have been studied for their potential use as biomarkers of physiological processes and disease states.

It's worth noting that androstadienes are sometimes referred to as "androstenes" in the literature, although this term can also refer to other related compounds.

Protein kinases are a group of enzymes that play a crucial role in many cellular processes by adding phosphate groups to other proteins, a process known as phosphorylation. This modification can activate or deactivate the target protein's function, thereby regulating various signaling pathways within the cell. Protein kinases are essential for numerous biological functions, including metabolism, signal transduction, cell cycle progression, and apoptosis (programmed cell death). Abnormal regulation of protein kinases has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Phosphatidylinositol 3-Kinase (PI3K) is an intracellular lipid kinase that phosphorylates the 3-hydroxyl group of the inositol ring of phosphatidylinositol and its phosphorylated derivatives, converting PIP2 (phosphatidylinositol 4,5-bisphosphate) to PIP3 (phosphatidylinositol 3,4,5-trisphosphate). This enzyme plays a crucial role in various cellular functions such as cell growth, proliferation, differentiation, motility, survival, and intracellular trafficking. PI3Ks are classified into three classes (I, II, and III) based on their structure, regulation, and substrate specificity. Class I PI3Ks are further divided into two subclasses (IA and IB), which are involved in signal transduction downstream of receptor tyrosine kinases and G protein-coupled receptors. Dysregulation of PI3K signaling has been implicated in various human diseases, including cancer, diabetes, and autoimmune disorders.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

I'm sorry for any confusion, but "Morpholines" is not a medical term. It is a chemical term that refers to a class of heterocyclic organic compounds containing one nitrogen atom and one oxygen atom in the ring. They are widely used as intermediates in the synthesis of various pharmaceuticals, agrochemicals, and dyes. If you have any questions about a medical issue or term, I'd be happy to try to help answer those for you!

Protein-kinase B, also known as AKT, is a group of intracellular proteins that play a crucial role in various cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. The AKT family includes three isoforms: AKT1, AKT2, and AKT3, which are encoded by the genes PKBalpha, PKBbeta, and PKBgamma, respectively.

Proto-oncogene proteins c-AKT refer to the normal, non-mutated forms of these proteins that are involved in the regulation of cell growth and survival under physiological conditions. However, when these genes are mutated or overexpressed, they can become oncogenes, leading to uncontrolled cell growth and cancer development.

Activation of c-AKT occurs through a signaling cascade that begins with the binding of extracellular ligands such as insulin-like growth factor 1 (IGF-1) or epidermal growth factor (EGF) to their respective receptors on the cell surface. This triggers a series of phosphorylation events that ultimately lead to the activation of c-AKT, which then phosphorylates downstream targets involved in various cellular processes.

In summary, proto-oncogene proteins c-AKT are normal intracellular proteins that play essential roles in regulating cell growth and survival under physiological conditions. However, their dysregulation can contribute to cancer development and progression.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

Protein kinase inhibitors (PKIs) are a class of drugs that work by interfering with the function of protein kinases. Protein kinases are enzymes that play a crucial role in many cellular processes by adding a phosphate group to specific proteins, thereby modifying their activity, localization, or interaction with other molecules. This process of adding a phosphate group is known as phosphorylation and is a key mechanism for regulating various cellular functions, including signal transduction, metabolism, and cell division.

In some diseases, such as cancer, protein kinases can become overactive or mutated, leading to uncontrolled cell growth and division. Protein kinase inhibitors are designed to block the activity of these dysregulated kinases, thereby preventing or slowing down the progression of the disease. These drugs can be highly specific, targeting individual protein kinases or families of kinases, making them valuable tools for targeted therapy in cancer and other diseases.

Protein kinase inhibitors can work in various ways to block the activity of protein kinases. Some bind directly to the active site of the enzyme, preventing it from interacting with its substrates. Others bind to allosteric sites, changing the conformation of the enzyme and making it inactive. Still, others target upstream regulators of protein kinases or interfere with their ability to form functional complexes.

Examples of protein kinase inhibitors include imatinib (Gleevec), which targets the BCR-ABL kinase in chronic myeloid leukemia, and gefitinib (Iressa), which inhibits the EGFR kinase in non-small cell lung cancer. These drugs have shown significant clinical benefits in treating these diseases and have become important components of modern cancer therapy.

Calcium-calmodulin-dependent protein kinases (CAMKs) are a family of enzymes that play a crucial role in intracellular signaling pathways. They are activated by the binding of calcium ions and calmodulin, a ubiquitous calcium-binding protein, to their regulatory domain.

Once activated, CAMKs phosphorylate specific serine or threonine residues on target proteins, thereby modulating their activity, localization, or stability. This post-translational modification is essential for various cellular processes, including synaptic plasticity, gene expression, metabolism, and cell cycle regulation.

There are several subfamilies of CAMKs, including CaMKI, CaMKII, CaMKIII (also known as CaMKIV), and CaMK kinase (CaMKK). Each subfamily has distinct structural features, substrate specificity, and regulatory mechanisms. Dysregulation of CAMK signaling has been implicated in various pathological conditions, such as neurodegenerative diseases, cancer, and cardiovascular disorders.

SRC-family kinases (SFKs) are a group of non-receptor tyrosine kinases that play important roles in various cellular processes, including cell proliferation, differentiation, survival, and migration. They are named after the founding member, SRC, which was first identified as an oncogene in Rous sarcoma virus.

SFKs share a common structure, consisting of an N-terminal unique domain, a SH3 domain, a SH2 domain, a catalytic kinase domain, and a C-terminal regulatory tail with a negative regulatory tyrosine residue (Y527 in human SRC). In their inactive state, SFKs are maintained in a closed conformation through intramolecular interactions between the SH3 domain, SH2 domain, and the phosphorylated C-terminal tyrosine.

Upon activation by various signals, such as growth factors, cytokines, or integrin engagement, SFKs are activated through a series of events that involve dephosphorylation of the regulatory tyrosine residue, recruitment to membrane receptors via their SH2 and SH3 domains, and trans-autophosphorylation of the activation loop in the kinase domain.

Once activated, SFKs can phosphorylate a wide range of downstream substrates, including other protein kinases, adaptor proteins, and cytoskeletal components, thereby regulating various signaling pathways that control cell behavior. Dysregulation of SFK activity has been implicated in various diseases, including cancer, inflammation, and neurological disorders.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Protein Kinase C (PKC) is a family of serine-threonine kinases that play crucial roles in various cellular signaling pathways. These enzymes are activated by second messengers such as diacylglycerol (DAG) and calcium ions (Ca2+), which result from the activation of cell surface receptors like G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs).

Once activated, PKC proteins phosphorylate downstream target proteins, thereby modulating their activities. This regulation is involved in numerous cellular processes, including cell growth, differentiation, apoptosis, and membrane trafficking. There are at least 10 isoforms of PKC, classified into three subfamilies based on their second messenger requirements and structural features: conventional (cPKC; α, βI, βII, and γ), novel (nPKC; δ, ε, η, and θ), and atypical (aPKC; ζ and ι/λ). Dysregulation of PKC signaling has been implicated in several diseases, such as cancer, diabetes, and neurological disorders.

Enzyme activation refers to the process by which an enzyme becomes biologically active and capable of carrying out its specific chemical or biological reaction. This is often achieved through various post-translational modifications, such as proteolytic cleavage, phosphorylation, or addition of cofactors or prosthetic groups to the enzyme molecule. These modifications can change the conformation or structure of the enzyme, exposing or creating a binding site for the substrate and allowing the enzymatic reaction to occur.

For example, in the case of proteolytic cleavage, an inactive precursor enzyme, known as a zymogen, is cleaved into its active form by a specific protease. This is seen in enzymes such as trypsin and chymotrypsin, which are initially produced in the pancreas as inactive precursors called trypsinogen and chymotrypsinogen, respectively. Once they reach the small intestine, they are activated by enteropeptidase, a protease that cleaves a specific peptide bond, releasing the active enzyme.

Phosphorylation is another common mechanism of enzyme activation, where a phosphate group is added to a specific serine, threonine, or tyrosine residue on the enzyme by a protein kinase. This modification can alter the conformation of the enzyme and create a binding site for the substrate, allowing the enzymatic reaction to occur.

Enzyme activation is a crucial process in many biological pathways, as it allows for precise control over when and where specific reactions take place. It also provides a mechanism for regulating enzyme activity in response to various signals and stimuli, such as hormones, neurotransmitters, or changes in the intracellular environment.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Proto-oncogene proteins are normal cellular proteins that play crucial roles in various cellular processes, such as signal transduction, cell cycle regulation, and apoptosis (programmed cell death). They are involved in the regulation of cell growth, differentiation, and survival under physiological conditions.

When proto-oncogene proteins undergo mutations or aberrations in their expression levels, they can transform into oncogenic forms, leading to uncontrolled cell growth and division. These altered proteins are then referred to as oncogene products or oncoproteins. Oncogenic mutations can occur due to various factors, including genetic predisposition, environmental exposures, and aging.

Examples of proto-oncogene proteins include:

1. Ras proteins: Involved in signal transduction pathways that regulate cell growth and differentiation. Activating mutations in Ras genes are found in various human cancers.
2. Myc proteins: Regulate gene expression related to cell cycle progression, apoptosis, and metabolism. Overexpression of Myc proteins is associated with several types of cancer.
3. EGFR (Epidermal Growth Factor Receptor): A transmembrane receptor tyrosine kinase that regulates cell proliferation, survival, and differentiation. Mutations or overexpression of EGFR are linked to various malignancies, such as lung cancer and glioblastoma.
4. Src family kinases: Intracellular tyrosine kinases that regulate signal transduction pathways involved in cell proliferation, survival, and migration. Dysregulation of Src family kinases is implicated in several types of cancer.
5. Abl kinases: Cytoplasmic tyrosine kinases that regulate various cellular processes, including cell growth, differentiation, and stress responses. Aberrant activation of Abl kinases, as seen in chronic myelogenous leukemia (CML), leads to uncontrolled cell proliferation.

Understanding the roles of proto-oncogene proteins and their dysregulation in cancer development is essential for developing targeted cancer therapies that aim to inhibit or modulate these aberrant signaling pathways.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

p38 Mitogen-Activated Protein Kinases (p38 MAPKs) are a family of conserved serine-threonine protein kinases that play crucial roles in various cellular processes, including inflammation, immune response, differentiation, apoptosis, and stress responses. They are activated by diverse stimuli such as cytokines, ultraviolet radiation, heat shock, osmotic stress, and lipopolysaccharides (LPS).

Once activated, p38 MAPKs phosphorylate and regulate several downstream targets, including transcription factors and other protein kinases. This regulation leads to the expression of genes involved in inflammation, cell cycle arrest, and apoptosis. Dysregulation of p38 MAPK signaling has been implicated in various diseases, such as cancer, neurodegenerative disorders, and autoimmune diseases. Therefore, p38 MAPKs are considered promising targets for developing new therapeutic strategies to treat these conditions.

Protein-Tyrosine Kinases (PTKs) are a type of enzyme that plays a crucial role in various cellular functions, including signal transduction, cell growth, differentiation, and metabolism. They catalyze the transfer of a phosphate group from ATP to the tyrosine residues of proteins, thereby modifying their activity, localization, or interaction with other molecules.

PTKs can be divided into two main categories: receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs). RTKs are transmembrane proteins that become activated upon binding to specific ligands, such as growth factors or hormones. NRTKs, on the other hand, are intracellular enzymes that can be activated by various signals, including receptor-mediated signaling and intracellular messengers.

Dysregulation of PTK activity has been implicated in several diseases, such as cancer, diabetes, and inflammatory disorders. Therefore, PTKs are important targets for drug development and therapy.

Mitogen-Activated Protein Kinase 1 (MAPK1), also known as Extracellular Signal-Regulated Kinase 2 (ERK2), is a protein kinase that plays a crucial role in intracellular signal transduction pathways. It is a member of the MAPK family, which regulates various cellular processes such as proliferation, differentiation, apoptosis, and stress response.

MAPK1 is activated by a cascade of phosphorylation events initiated by upstream activators like MAPKK (Mitogen-Activated Protein Kinase Kinase) in response to various extracellular signals such as growth factors, hormones, and mitogens. Once activated, MAPK1 phosphorylates downstream targets, including transcription factors and other protein kinases, thereby modulating their activities and ultimately influencing gene expression and cellular responses.

MAPK1 is widely expressed in various tissues and cells, and its dysregulation has been implicated in several pathological conditions, including cancer, inflammation, and neurodegenerative diseases. Therefore, understanding the regulation and function of MAPK1 signaling pathways has important implications for developing therapeutic strategies to treat these disorders.

Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.

In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.

Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.

As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes 1BO1 and 2GK9. Kai M, ... PIP kinase, phosphatidylinositol 4-phosphate kinase, phosphatidylinositol-4-phosphate 5-kinase, and type I PIP kinase. This ... In enzymology, 1-phosphatidylinositol-4-phosphate 5-kinase (EC 2.7.1.68) is an enzyme that catalyzes the chemical reaction ATP ... the two substrates of this enzyme are ATP and 1-phosphatidyl-1D-myo-inositol 4-phosphate, whereas its two products are ADP and ...
PIK3R2 and PIP5K1A are two kinases that phosphorylate Phosphatidylinositol (PIP) providing PSD4 with substrates for its GTP ... which is a type of MHC class II deficiency. Like MHC class I molecules, class II molecules are also heterodimers, but in this ... The stable class II MHC is then presented on the cell surface. After MHC class II complexes are synthesized and presented on ... MHC class II expression is closely regulated in APCs by CIITA, which is the MHC class II transactivator. CIITA is solely ...
Class II PI 3-kinases also appear to synthesise PtdIns3P, their activity however appears to be regulated by a range of stimuli ... P2 by the lipid kinase PIKfyve. Both FYVE domains and PX domains - found in proteins such as SNX1, HGS, and EEA1 - bind to ... It is the product of both the class II and III phosphoinositide 3-kinases (PI 3-kinases) activity on phosphatidylinositol. ... Phosphatidylinositol 3-phosphate (PtdIns3P) is a phospholipid found in cell membranes that helps to recruit a range of proteins ...
This enzyme is also called type II PIP kinase. This enzyme participates in 3 metabolic pathways: inositol phosphate metabolism ... The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol-5-phosphate 4-phosphotransferase. ... In enzymology, a 1-phosphatidylinositol-5-phosphate 4-kinase (EC 2.7.1.149) is an enzyme that catalyzes the chemical reaction ... the two substrates of this enzyme are ATP and 1-phosphatidyl-1D-myo-inositol 5-phosphate, whereas its two products are ADP and ...
The PI3K family is divided into four different classes: Class I, Class II, Class III, and Class IV. The classifications are ... Class I PI3Ks catalyze the conversion of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) into phosphatidylinositol (3,4,5)- ... Class II and III PI3Ks are differentiated from the Class I by their structure and function. The distinct feature of Class II ... Class II comprises three catalytic isoforms (C2α, C2β, and C2γ), but, unlike Classes I and III, no regulatory proteins. Class ...
The ARF proteins are categorized as class I (ARF1, ARF2, and ARF3), class II (ARF4 and ARF5) and class III (ARF6). The members ... 1999). "Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle ... Shin OH, Couvillon AD, Exton JH (2001). "Arfophilin is a common target of both class II and class III ADP-ribosylation factors ... Shin OH, Ross AH, Mihai I, Exton JH (2000). "Identification of arfophilin, a target protein for GTP-bound class II ADP- ...
... class III phosphatidylinositol 3-kinase complex 2). Negative modulation of Rubicon is associated with reduction of aging and ... April 2009). "Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages". Nature ... lipid kinase inhibition, and autophagy suppression". The Journal of Biological Chemistry. 286 (1): 185-191. doi:10.1074/jbc. ... April 2009). "Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3- ...
This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3- ... Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing gamma polypeptide is an enzyme that in humans is encoded by the ... Rozycka M, Lu YJ, Brown RA, Lau MR, Shipley JM, Fry MJ (Feb 1999). "cDNA cloning of a third human C2-domain-containing class II ... 1998). "A novel class II phosphoinositide 3-kinase predominantly expressed in the liver and its enhanced expression during ...
This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3- ... Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing beta polypeptide is an enzyme that in humans is encoded by the ... Arcaro A, Zvelebil MJ, Wallasch C, Ullrich A, Waterfield MD, Domin J (Jun 2000). "Class II phosphoinositide 3-kinases are ... Wheeler M, Domin J (Oct 2001). "Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor ...
This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of Class II PI 3- ... Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing alpha polypeptide is an enzyme that in humans is encoded by the ... 2000). "The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin- ... 2000). "Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors". Mol. Cell ...
... the two substrates of this enzyme are ATP and 1-phosphatidyl-1D-myo-inositol 4-phosphate, whereas its two products are ADP and ... The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol-4-phosphate 3-phosphotransferase. Other names in ... In enzymology, a phosphatidylinositol-4-phosphate 3-kinase (EC 2.7.1.154) is an enzyme that catalyzes the chemical reaction ATP ... This enzyme participates in phosphatidylinositol signaling system. As of late 2007, 3 structures have been solved for this ...
The age-1 gene encodes the catalytic subunit of class-I phosphatidylinositol 3-kinase (PI3K). A decade after Johnson's ... one of the two genes that are essential for dauer larva formation, was shown by Cynthia Kenyon to double C. elegans lifespan. ... and tyrosine kinase-related pathways. They then used drugs known to target the identified pathways and showed these drugs kill ... Kenyon showed that the daf-2 mutants, which would form dauers above 25 °C (298 K; 77 °F) would bypass the dauer state below 20 ...
Class I and II phosphoinositide 3-kinases (PI3Ks) synthesize PtdIns(3,4)P2 by phosphorylating the phosphoinositide PI4P's 3-OH ... phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα. Current Biology. 1997;7(4). ... P2 in class I and II PI3K-regulated pathways. Biochem Soc Trans. (2016) 44:307-14. 10.1042/BST20150248 Krause M, Leslie JD, ... phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα. Current Biology. 1997;7(4). ...
"Association of T cell antigen CD7 with type II phosphatidylinositol-4 kinase, a key component in pathways of inositol phosphate ... Bevec T, Stoka V, Pungercic G, Dolenc I, Turk V (April 1996). "Major histocompatibility complex class II-associated p41 ... Aruffo A, Seed B (November 1987). "Molecular cloning of two CD7 (T-cell leukemia antigen) cDNAs by a COS cell expression system ... Lee DM, Patel DD, Pendergast AM, Haynes BF (August 1996). "Functional association of CD7 with phosphatidylinositol 3-kinase: ...
... some phosphatidylinositol 4-kinases, myosin light chain kinase (MLCK) and mitogen-activated protein kinase (MAPK) at high ... It displays a similar potency in vitro for the class I, II, and III PI3K members although it can also inhibit other PI3K- ... In 2010, sonolisib was starting 4 phase II trials for solid tumors. The company gave an update on its phase 2 trials in Jun ... September 2015). "Phase II study of PX-866 in recurrent glioblastoma". Neuro-Oncology. 17 (9): 1270-4. doi:10.1093/neuonc/ ...
... and protein kinase C activity. Two enzymes, CDP-diacylglycerol synthase and phosphatidylinositol synthase, are involved in the ... Phosphatidylinositol synthase, a member of the CDP-alcohol phosphatidyl transferase class-I family, is an integral membrane ... Phosphatidylinositol breakdown products are ubiquitous second messengers that function downstream of multiple G protein-coupled ... Antonsson B (1997). "Phosphatidylinositol synthase from mammalian tissues". Biochim. Biophys. Acta. 1348 (1-2): 179-86. doi: ...
... phosphatidylinositol 4-kinase, phosphatidylinositol kinase, type II phosphatidylinositol kinase, PI kinase, and PI 4-kinase. ... The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol 4-phosphotransferase. Other names in common use ... "Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate". Nature. 332 (6165): ... In enzymology, a 1-phosphatidylinositol 4-kinase (EC 2.7.1.67) is an enzyme that catalyzes the chemical reaction ATP + 1- ...
All NKG2D ligands are homologous to MHC class I molecules and are divided into two families: MIC and RAET1/ULBP. Human MIC ... Ligation of sensor kinases ATM and ATR leads to activation of different checkpoint kinases, such as Chk1 and Chk2, which are ... "NKG2D induces Mcl-1 expression and mediates survival of CD8 memory T cell precursors via phosphatidylinositol 3-kinase". ... viral replication or some viral products activate the ATM and ATR kinases. These kinases initiate the DNA damage response ...
It downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also ... CD28-associated IL-10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3-kinase binding". FASEB Journal ... IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins. Consequently, ... IL-10 is classified as a class-2 cytokine, a set of cytokines including IL-19, IL-20, IL-22, IL-24 (Mda-7), IL-26 and ...
In phase II clinical trials: Apitolisib (codenamed GDC-0980, GNE 390, RG7422; pan-class I PI3K and mTOR inhibitor) has ... January 2015). "First-in-human phase I study of pictilisib (GDC-0941), a potent pan-class I phosphatidylinositol-3-kinase (PI3K ... Two single-arm trials (in CLL and iNHL) have reported results. Voxtalisib (codenamed SAR245409, XL765; pan-class I PI3K ... Pictilisib (codenamed GDC-0941; pan-class I PI3K inhibitor) has undergone five phase II trials as a potential treatment for ...
... scavenger receptor class B type I (SR-BI) and lysosomal integral membrane protein II (LIMP-II). CD36 interacts with a number of ... Bull HA, Brickell PM, Dowd PM (August 1994). "Src-related protein tyrosine kinases are physically associated with the surface ... Unlike macropinocytosis this process is not affected by inhibitors of phosphatidylinositol 3-kinase or Na+/H+ exchange. CD36 ... In addition a role for CD36 has been found in the clearance of gametocytes (stages I and II). CD36 has been shown to have a ...
As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes 1INP and 1JP4. Berridge MJ ... This enzyme participates in inositol phosphate metabolism and phosphatidylinositol signaling system. ... J. 212 (2): 473-82. doi:10.1042/bj2120473. PMC 1152070. PMID 6309146. Connolly TM, Bansal VS, Bross TE, Irvine RF, Majerus PW ( ... Portal: Biology v t e (EC 3.1.3, Enzymes of known structure, All stub articles, EC 3.1 stubs). ...
July 2021). "Absorption, metabolism and excretion of pictilisib, a potent pan-class I phosphatidylinositol-3-Kinase (PI3K) ... It features two consecutive reactions; these are Cu-catalysed C-N coupling reactions. The route for synthesis involves multiple ... Inavolisib shows increased selectivity, limiting the amount of non-PI3K family kinases it inhibits to only one. Further, when ... The class I isoform PI3K alpha (PI3Kα) is often times expressed in solid tumours through gene amplification or activated ...
PIP2 can also be formed by type II phosphatidylinositol 5-phosphate 4-kinases from PI(5)P. The fatty acids of PIP2 are variable ... Class I PI 3-kinases phosphorylate PtdIns(4,5)P2 forming phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) and ... 2005). "Phosphatidylinositol phosphate kinase type Iγ regulates dynamics of large dense-core vesicle fusion". PNAS. 102 (14): ... PIP2 is formed primarily by the type I phosphatidylinositol 4-phosphate 5-kinases from PI(4)P. In metazoans, ...
Phosphatidyl inositol phosphates (PIPs), one of the most important lipid signaling molecules, is found to differ as the ... Felder S, Miller K, Moehren G, Ullrich A, Schlessinger J, Hopkins CR (May 1990). "Kinase activity controls the sorting of the ... However, several observations (described above) have now demonstrated that it is more likely that transport between these two ... Another unique identifying feature that differs between the various classes of endosomes is the lipid composition in their ...
In vivo Vps34 can phosphorylate only phosphatidylinositol to form phosphatidylinositol (3)-phosphate (PtdIns(3)P). Vps34 was ... Vps34 has been shown to interact with Vps15 (PIK3R4, p150), a protein kinase. Vps15 can activate the lipid kinase activity of ... Class III PI 3-kinase is a subgroup of the enzyme family, phosphoinositide 3-kinase that share a common protein domain ... There is only one known class III PI 3-kinase, Vps34, which is also the only PI 3-kinase expressed in all eukaryotic cells. In ...
... like protein kinase, proliferating cell nuclear antigen (PCNA)-like group, two serine/threonine(S/T) kinases and their adaptors ... A class of checkpoint mediator proteins including BRCA1, MDC1, and 53BP1 has also been identified. These proteins seem to be ... Checkpoint Proteins can be separated into four groups: phosphatidylinositol 3-kinase (PI3K)- ... First, two kinases, ATM and ATR are activated within 5 or 6 minutes after DNA is damaged. This is followed by phosphorylation ...
This similarity increases to ~ 70% across PKCs and even higher when comparing within classes. For example, the two atypical PKC ... It is presumed that this is achieved by the production of diacylglycerol from phosphatidylinositol by a phospholipase; fatty ... The term "protein kinase C" usually refers to the entire family of isoforms. The different classes of PKCs found in jawed ... In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are ...
Dual-specificity kinases are subclass of the tyrosine kinases. mTOR is a kinase within the family of phosphatidylinositol-3 ... protein kinases are classified in two major categories based on their substrate specificity, protein tyrosine kinases and ... November 2011). "Discovery of a potent, selective, and orally available class I phosphatidylinositol 3-kinase (PI3K)/mammalian ... The serine/threonine kinase mTOR is a downstream effector of the PI3K/AKT pathway, and forms two distinct multiprotein ...
The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol-3-phosphate 5-phosphotransferase. Other names in ... the two substrates of this enzyme are ATP and 1-phosphatidyl-1D-myo-inositol 3-phosphate, whereas its two products are ADP and ... In enzymology, a 1-phosphatidylinositol-3-phosphate 5-kinase (EC 2.7.1.150) is an enzyme that catalyzes the chemical reaction ... common use include type III PIP kinase, and phosphatidylinositol 3-phosphate 5-kinase. This enzyme participates in ...
As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes 1BO1 and 2GK9. Kai M, ... PIP kinase, phosphatidylinositol 4-phosphate kinase, phosphatidylinositol-4-phosphate 5-kinase, and type I PIP kinase. This ... In enzymology, 1-phosphatidylinositol-4-phosphate 5-kinase (EC 2.7.1.68) is an enzyme that catalyzes the chemical reaction ATP ... the two substrates of this enzyme are ATP and 1-phosphatidyl-1D-myo-inositol 4-phosphate, whereas its two products are ADP and ...
This gene provides instructions for making slightly different versions of another protein; the most common version is called ... Singh A, Joshi V, Jindal AK, Mathew B, Rawat A. An updated review on activated PI3 kinase delta syndrome (APDS). Genes Dis. ... Both p110δ and p85α are pieces (subunits) of an enzyme called phosphatidylinositol 3-kinase (PI3K), which turns on signaling ... There are two types of activated PI3K-delta syndrome, each with different genetic causes. ...
... from nine scaffold classes: I) histamine analogs (e.g., 4-methylhistamine), II) triazoles, III) guanidines [e.g., 2-(2- ... extracellular signal-regulated kinase. PTx. pertussis toxin. EFC. enzyme fragment complementation. JNJ 7777120. 1-[(5-chloro-1H ... Analysis of Multiple Histamine H4 Receptor Compound Classes Uncovers Gαi Protein- and β-Arrestin2-Biased Ligands. Saskia ... On the basis of distinct efficacy values between the two assays, we identified hH4R ligands that are biased toward the Gαi- ...
We find that Oral-Facial-Digital syndrome 1 functions as a class II Nucleation promoting factor to promote Arp2/3 complex- ... tubulin beta class I; ULK1: unc-51 like autophagy activating kinase 1; VPS41: VPS41, HOPS complex subunit; WB: western blot; WT ... class III phosphatidylinositol 3-kinase; SQSTM1/p62: sequestosome 1; RAB2: RAB2A, member RAS oncogene family; RAB7: RAB7A, ... In cells without IFT20 or CEP164, two genes encoding key factors for ciliogenesis, depletion of TCHP still led to G0 arrest. ...
Protein and lipid kinases are two important classes of biomedically relevant enzymes. The expression and activity of many ... ATR, a phosphatidylinositol kinase-related protein homologous to ataxia telangiectasia mutated (ATM), is important for the ... NEK8/NPHP9 is a ciliary kinase associated with two renal ciliopathies in humans and mice, nephronophthisis (NPHP) and ... In yeast, Rad5-mediated damage avoidance and Rad18-mediated translesion synthesis (TLS) are two forms of PRR. Two Rad5-related ...
Activated tyrosine kinases generate a second wave of messengers by activating serine/threonine kinases or phosphatase pathways ... Immunoglobulin class-switching requires the interaction of CD40 with CD40 ligand (or gp39) present on the surface of B and T ... Two patients survived, and clinical and cerebrospinal fluid abnormalities resolved. Hearing loss due to chronic otitis media or ... Three major pathways have been identified: the inositol phospholipid hydrolysis pathway, the phosphatidyl inositol-3-kinase ...
... elegans and an absence of AKT-2 and DDL-2 homologs from H. contortus. Interestingly, DAF-16 has a single isoform in H. ... Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis ... only two kinases were predicted downstream of Hc-PDK-1, namely Hc-AKT-1 and Hc-SGK-1. The absence of AKT-2 might indicate a ... Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) is the product of the class I phosphoinostide 3-kinases (PI 3-kinases) ...
Compound class: Synthetic organic Comment: AZD8154 is one of the chemical structures in a patent from AstraZeneca that claims ... dual phosphatidylinositol 3-kinase (PI3K) δ/γ inhibitors [1]. Its discovery was formally disclosed by Perry et al., in June ... 3,35)36/h4,6-7,12-13,16-17H,5,8-11,14H2,1-3H3,(H,28,29,30)/t16-/m0/s1 ... 2021 [2]. Ligand Activity Visualisation Charts. These are box plot that provide a unique visualisation, summarising all the ...
For patient education information, see the Thyroid Cancer Directory. Patient education information on thyroid cancer is also ... Adenomas and follicular carcinomas of the thyroid display two major patterns of chromosomal changes. J Pathol. 2005 Jul. 206(3 ... is thought to be initiated by point mutations that result in dysregulation of the phosphatidylinositol-3 kinase (PI3K)/AKT ... The incidence is higher in women than men by a factor of 2-3 or more. The ratio varies by patient age:. * In patients younger ...
Do Others Online Classes For Money. Those involved cell signaling are mediated by the transcription factor-to-intrinsic signal ... At least, the growth of nitroso compounds starts with the expression of gene expression controlled from DNA by two ... and mitogen-activated protein kinase (MAPK) pathways. Many other questions remain, however. The most basic of these is how the ... in DNA replication and translation by including transcription factors involved in many things such as phosphatidylinositol 3 ...
... an orally available pan-class I phosphatidylinositol 3-kinase (PIK3) inhibitor.[7] The median PFS, overall response rate, and ... In two cases, the researchers performed synchronous biopsies, confirming genome-wide representation of the tumor genome in ... positive breast cancer receiving two lines of targeted therapy over 3 years.[5] The researchers characterized genomic ... exome sequencing was performed on two to five plasma samples (19 in total) spanning multiple courses of treatment, at selected ...
phosphatidylinositol-4-phosphate 5.... PKN2. 5586. PKN2. protein kinase N2 [Source:HGNC Sym.... ... POU class 5 homeobox 1 [Source:HGN.... PPA2. 27068. PPA2. inorganic pyrophosphatase 2 [Sourc.... ...
The crystal structure of the SAM domain from an Eph receptor tyrosine kinase, EphB2, reveals two large interfaces. In one ... Together, these results suggest that Smaug and Vts1 define a larger class of post-transcriptional regulators that act in part ... Phosphatidylinositol signaling system. 4.79. map00564. Glycerophospholipid metabolism. 4.79. map00561. Glycerolipid metabolism ... Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction ...
In vitro kinase assay. An in vitro BRAF activation kinase assay was conducted according to the instructions provided by ... Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and ... a PI3K kinase inhibitor, were mixed with the substrate phosphatidylinositol and then incubated with a [γ32P] ATP mixture. The ... and other candidate kinases, which included the previously predicted targeted kinases. Kinase profiling was performed by ...
Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer. 2010;10:825-41 ... Although these two pathways are not identical, they share several steps. In glycolysis, glucose is broken down into two ... the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Educa ... phosphatidylinositol 3-kinase (PI3K), and NOTCH were reported to be causes of these alterations [1]. ...
"Phosphatidylinositol-5-phosphate 4-kinases (PIP4ks) can be a family of lipid kinases which especially use phosphatidylinositol ... Moreover, the vascularization with the PMCS class is a lot more apparent in contrast to the other two groupings. The actual use ... A overall of two,095 successive joint MR photo studies from your Twenty-two calendar month period of time were retrospectively ... Settings: Two colleges and 2 main proper care trusts.. Participant: Throughout Stage 1 17 first-time moms in addition to their ...
Redistribution of Brutons tyrosine kinase by activation of phosphatidylinositol 3-kinase and Rho-family GTPases. ... MHC class I mosaic mice reveal insights into control of Ly49C inhibitory receptor expression in NK cells. ... Cardona ME; Simonson OE; Oprea II; Moreno PMD; Silva-Lara MF; Mohamed AJ; Christensson B; Gahrton G; Dilber MS; Smith CIE; ... Brutons tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. ...
Activated tyrosine kinases generate a second wave of messengers by activating serine/threonine kinases or phosphatases pathways ... Immunoglobulin class-switching requires the interaction of CD40 with CD40 ligand (or gp39) present on the surface of B and T ... Three major pathways have been identified: the inositol phospholipid hydrolysis pathway, the phosphatidyl inositol-3-kinase ... The BTK gene is present on Xq21.3-q22, and its defect results in deficiency of Bruton tyrosine kinase. Non-XLA is the result of ...
protein serine/threonine kinase activity protein kinase C binding protein binding ATP binding ... positive regulation of transcription from RNA polymerase II promoter positive regulation of glucose import positive regulation ... and acts as a transducer of many functions initiated by growth factor receptors that activate phosphatidylinositol 3-kinase (PI ... rac protein kinase beta; RAC-beta serine/threonine-protein kinase; RAC-PK-beta; v-akt murine thymoma viral oncogene homolog 2 ...
Discovery of 4-sulfamoyl-phenyl-β-lactams as a new class of potent carbonic anhydrase isoforms I, II, IV and VII inhibitors: ... In vivo detection of early tumor response to tyrosine kinase inhibitors by microSPECT with 99mTc-MIBI (432 views). Eur J Nucl ... Inhibition of p85, the non-catalytic subunit of phosphatidylinositol 3-kinase, exerts potent antitumor activity in human breast ... Discovery of 4-sulfamoyl-phenyl-beta-lactams as a new class of potent carbonic anhydrase isoforms I, II, IV and VII inhibitors ...
Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2:561-6 ... there were only two probes containing two genes significant differentially expressed in increment of pT stage and metastatic ... it could stimulate phosphatidylinositol 3-kinase (PI3K) and STAT, ensuing activation of the STAT pathway [14]. Despite this ... File import instruction ... the ras/mitogen-activated protein kinase (MAP kinase) pathway [ ...
Forty-two SLiMs were identified (Figure 5). In the top 10 most frequently identified motifs was the SLiM LIG_PDZ_Class_2, which ... Receptor-like Kinases from Arabidopsis Form a Monophyletic Gene Family Related to Animal Receptor Kinases. Proc. Natl. Acad. ... This motif is a docking site for multiple phosphatidylinositol-3 kinase-related kinases (PIKKs) involved in cell cycle DNA ... two proteins for SAP11, two for Zaofeng effectors, two for ncSecPs, etc). The sequences, in a FASTA file, were submitted to the ...
Phase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including ... Phase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including ... Protein kinase B (PKB/AKT)/Glycogen synthase kinase-3 beta (GSK3B) axis (Yadav et al., 2013b). ... Phase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including ...
ii) The myocardial architecture in HF rats was improved with probiotic administration. iii) The two major apoptotic pathways in ... You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may ... Table II. Analysis of blood biochemistry of Wistar rats fed with a normal diet, high-fat diet and different concentrations of ... Table II. Analysis of blood biochemistry of Wistar rats fed with a normal diet, high-fat diet and different concentrations of ...
In complementation group A, class II transcription activator (CIITA) is mutated. CIITA is a positive regulator of MHC class II ... JAK3 is a tyrosine kinase composed of seven JAK homology (JH) domains. JH1 is the kinase domain and JH2 a kinase-like module. ... Pleckstrin homology (PH) domain is responsible for membrane localisation of the protein by binding to the phosphatidyl inositol ... MHC class II deficiencies impair transcription of MHC II genes. Three forms have been found. Proteins in these groups are parts ...
RT1 class II, locus Ba. susceptibility. ISO. DNA:polymorphisms: :HLA-DQA1*01:03, HLA-DQA1*03:02 (human). RGD. PMID:26856406. ... Janus kinase 3. ISO. RGD. PMID:22363534. RGD:11531103. NCBI chr16:18,386,330...18,398,542 Ensembl chr16:18,386,405...18,398,536 ... phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma. ISO. RGD. PMID:25775137. RGD:38599200. NCBI chr 6: ... protein kinase AMP-activated catalytic subunit alpha 2. ISO. mRNA:decreased expression:brain (mouse). RGD. PMID:29107705. RGD: ...
RESULTS:HSDL2 expression was upregulated in human ovarian cancer samples and in 3 human ovarian cancer cell lines: SKOV3, ... Abnormal lipometabolism in peroxisomes is involved in tumor progression and hydroxysteroid dehydrogenase-like 2 (HSDL2), ... HO8910, and OVCAR-3. Higher expression of HSDL2 in ovarian tumor samples was associated with more progressed tumors (P=0.03) ... it promoted cell apoptosis and resulted in cell cycle arrest at the G0/G1 phase in human ovarian cancer cell lines OVCAR-3 and ...
The remaining two of the nine agents showed negative correlation with the query profiles. Tretinoin (retinoic acid) stimulated ... Thioridazine was a member of the class of phenothiazines that act, in part, by inhibiting respiration and lead to hypoxia [27 ... particularly those of phosphatidylinositol. Therefore, fulvestrant, as estrogen blocker might activate phospholipid pathway to ... The KS score indicated the similarity of two samples. For each GOM, it showed genes that had the same or reverse pattern of ...
  • There are two types of activated PI3K-delta syndrome, each with different genetic causes. (medlineplus.gov)
  • Activated PI3K-delta syndrome type 1 is caused by variants in the PIK3CD gene, which provides instructions for making a protein called p110 delta (p110δ). (medlineplus.gov)
  • Activated PI3K-delta syndrome type 2 is caused by variants in the PIK3R1 gene. (medlineplus.gov)
  • Both p110δ and p85α are pieces (subunits) of an enzyme called phosphatidylinositol 3-kinase (PI3K), which turns on signaling pathways within cells. (medlineplus.gov)
  • The molecular pathogenesis of follicular thyroid carcinoma (FTC) is thought to be initiated by point mutations that result in dysregulation of the phosphatidylinositol-3 kinase (PI3K)/AKT signaling pathway. (medscape.com)
  • Pituitary tumor-transforming gene (PTTG), GATA, signal transducer, and activator of transcription (STAT), phosphatidylinositol 3-kinase (PI3K), and NOTCH were reported to be causes of these alterations [ 1 ]. (medsci.org)
  • During the transient loss of p38 activity there was a temporary Fas-induced increase in phosphatidylinositol 3-kinase (PI3K) activity, which also had a pro-apoptotic impact on the neutrophils. (lu.se)
  • Following B-cell receptor activation, 2 waves of tyrosine kinase phosphorylation occur. (medscape.com)
  • the second activates Bruton tyrosine kinase and Syk. (medscape.com)
  • The BTK gene is present on Xq21.3-q22, and its defect results in deficiency of Bruton tyrosine kinase. (medscape.com)
  • JAK2 is a member of the class I type tyrosine kinase family of enzymes and is involved in signal transduction for erythropoietin , thrombopoietin, and granulocyte colony-stimulating factor (G-CSF) receptors among other entities. (msdmanuals.com)
  • In particular, the isothiourea class shows very diverse results, varying from Gα i protein-biased or β-arrestin2-biased to nonbiased antagonists upon minor structural changes. (aspetjournals.org)
  • One such protein is Nek8/NPHP9, a protein kinase we have shown to prevent DNA damage at stalled forks by regulating CDK activity. (stanford.edu)
  • BCL2 interacting protein 3 like [S. (gsea-msigdb.org)
  • Smaug, a protein that helps to establish a morphogen gradient in Drosophila embryos by repressing the translation of nanos (nos) mRNA, binds to the 3' untranslated region (UTR) of nos mRNA via two similar hairpin structures. (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing SAM domain in the selected taxonomic class. (embl.de)
  • AKT2 is a phosphoinositide-dependent serine/threonine protein kinase that is enriched in insulin responsive tissues and has been implicated in the metabolic actions of the hormone. (thermofisher.com)
  • Fas ligand and death receptor protein levels, as well as activities of caspase-8 and caspase-3, were significantly upregulated in hearts from obese rats, suggesting the involvement of Fas receptor-dependent apoptosis in obesity-associated heart disease ( 13 ). (spandidos-publications.com)
  • The acute cardioprotective effect of cannabinoids is mediated by activation of protein kinase C, extracellular signal-regulated kinase, and p38 kinase. (thctotalhealthcare.com)
  • The delayed cardioprotective effect of cannabinoid anandamide is mediated via stimulation of phosphatidylinositol-3-kinase-Akt signaling pathway and enhancement of heat shock protein 72 expression. (thctotalhealthcare.com)
  • Using two different methods it was possible to detect constitutive activity of p38 mitogen-activated protein kinase (p38) in newly isolated neutrophils. (lu.se)
  • The results in this dissertation also demonstrate that the protein phosphatase type 2A (PP2A) can directly and independently decrease the phosphorylation levels of both p38 and caspase 3. (lu.se)
  • Comparison of viral RNA-host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2. (cdc.gov)
  • Less pronounced severity of immunodeficiency can be due to a novel 2 bp-deletion (c.3222_3223delTG) in the final exon of AP3B1, causing a frameshift and thus a prolonged altered HPS2 protein. (medscape.com)
  • Hermansky-Pudlak syndrome type 5 (HPS-5) results from a deficiency of the HPS-5 protein, a component of BLOC-2. (medscape.com)
  • Bithiazole Inhibitors of Phosphatidylinositol 4-Kinase (PI4KIIIβ) as Broad-Spectrum Antivirals Blocking the Replication of SARS-CoV-2, Zika Virus and Human Rhinoviruses. (cdc.gov)
  • Treatment is often supportive, but Janus kinase 2 ( JAK2 ) inhibitors, such as ruxolitinib , fedratinib , pacritnib, or momelotinib may decrease symptoms, and stem cell transplantation may be curative. (msdmanuals.com)
  • A common trend in pathway preference for the nine different ligand classes could not be observed. (aspetjournals.org)
  • Three major pathways have been identified: the inositol phospholipid hydrolysis pathway, the phosphatidyl inositol-3-kinase pathway, and the Ras pathway. (medscape.com)
  • Together, these findings strongly suggest that oral administration of probiotics may attenuate cardiomyocyte apoptosis by activation of the phosphatidylinositol‑3 kinase/AKT survival‑signalling pathway in obese rats. (spandidos-publications.com)
  • In this study, a total of six genes and two proteins involved in the oocyte meiosis, the estrogen signaling pathway, progesterone-mediated oocyte maturation and the GnRH signaling pathway were identified. (researchsquare.com)
  • Those involved cell signaling are mediated by the transcription factor-to-intrinsic signal transducer and activator of transcription 3 (STAT3). (hiresomeonetodo.com)
  • Mutations of the Janus kinase 2 ( JAK2 ) gene are present in a high proportion of cases of primary myelofibrosis. (msdmanuals.com)
  • In enzymology, 1-phosphatidylinositol-4-phosphate 5-kinase (EC 2.7.1.68) is an enzyme that catalyzes the chemical reaction ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate ⇌ {\displaystyle \rightleftharpoons } ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate Thus, the two substrates of this enzyme are ATP and 1-phosphatidyl-1D-myo-inositol 4-phosphate, whereas its two products are ADP and 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate. (wikipedia.org)
  • The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol-4-phosphate 5-phosphotransferase. (wikipedia.org)
  • This enzyme participates in 3 metabolic pathways: inositol phosphate metabolism, phosphatidylinositol signaling system, and regulation of the actin cytoskeleton. (wikipedia.org)
  • Activated tyrosine kinases generate a second wave of messengers by activating serine/threonine kinases or phosphatases pathways. (medscape.com)
  • In addition, my experiments showed that the active form of p38 associates with caspase 8 and caspase 3, which is necessary for p38-induced phosphorylation of serine-362 and serine-150 on these caspases. (lu.se)
  • As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes 1BO1 and 2GK9. (wikipedia.org)
  • Upon nuclease digestion, the enzymes RNAP and RNAPC perform nucleotide triphosphate synthetase (NDS) activity in reaction between the two transcription factors and the nucleotide triphosphate triphosphohydrolase (HDP). (hiresomeonetodo.com)
  • Phase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including toxicants and drugs. (frontiersin.org)
  • These biochemical modifications impair the activities, and possibly also the stability, of caspase 8 and 3 and thereby weaken the capacity of these enzymes to induce apoptosis. (lu.se)
  • Dawson highlighted a study that followed a single patient with metastatic estrogen receptor (ER)-positive, HER2- positive breast cancer receiving two lines of targeted therapy over 3 years. (medscape.com)
  • The B-cell receptor is formed from the noncovalent association between surface IgM or IgD and 2 transmembrane proteins, IgA and immunoglobulin B. The presence of CD22 and CD19/CD21 on the cell surface, playing the role of coreceptorlike molecules, is necessary for the activation of the receptor. (medscape.com)
  • In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. (embl.de)
  • Through data mining a published transcriptomic database of UBUCs (GSE32894), it identified Colony Stimulating Factor 2 ( CSF2 ) as the stepwise upregulated gene of much significance among those related to the positive regulation of tyrosine phosphorylation of STAT5 (GO:0042523). (jcancer.org)
  • WIN55,212-2 induces cytoplasmic vacuolation in apoptosis-resistant MCL cells. (ki.se)
  • HPS-2 is caused by a mutation in the gene encoding the beta-3A subunit of the heterotetrameric AP3 complex ( ADTB3A ), which resides on chromosome 5. (medscape.com)
  • Dynamics and Determinants of SARS-CoV-2 RT-PCR Testing on Symptomatic Individuals Attending Healthcare Centers during 2020 in Bahia, Brazil. (cdc.gov)
  • 2018. Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid Metabolism By Facilitating Autophagy. . (cornell.edu)
  • Consequently, PP2A can increase the activity of caspase 3 by dual mechanisms and thereby promote the apoptotic response in human neutrophils. (lu.se)
  • Akt is involved in many cellular signaling pathways and acts as a transducer of many functions initiated by growth factor receptors that activate phosphatidylinositol 3-kinase (PI 3-kinase). (thermofisher.com)
  • Hence, we under- and growing public health challenge worldwide resulting from took our meta-analysis to estimate the effect of anthropometric rapid urbanization, excessive energy intake, developing obesity, risk factors on the prevalence of metabolic syndrome to inform re- and sedentary lifestyle habits (2). (cdc.gov)
  • A murine model of acute myeloid leukemia with Evi1 overexpression and autocrine stimulation by an intracellular form of GM-CSF in DA-3 cells. (ki.se)
  • [ 2 ] The absence of AP-3 results in a low intracellular content of neutrophil elastase, with the consequence of neutropenia. (medscape.com)
  • Dysfunction of cell cycle control and defects of primary ciliogenesis are two features of many cancers. (bvsalud.org)
  • Other names in common use include diphosphoinositide kinase, PIP kinase, phosphatidylinositol 4-phosphate kinase, phosphatidylinositol-4-phosphate 5-kinase, and type I PIP kinase. (wikipedia.org)
  • B and T cells, type 2 dendritic cells, and natural killer (NK) cells share a common ancestor: common lymphoid progenitor (CLP). (medscape.com)
  • collagen type IX alpha 2 chain [So. (gsea-msigdb.org)
  • Four such genes, HPS1, ADTB3A, HPS3, and HPS4, are associated with the 4 known subtypes of Hermansky-Pudlak syndrome: Hermansky-Pudlak syndrome type 1 (HPS-1), Hermansky-Pudlak syndrome type 2 (HPS-2), Hermansky-Pudlak syndrome type 3 (HPS-3), and Hermansky-Pudlak syndrome type 4 (HPS-4). (medscape.com)
  • Until October 2019, after two consecutive rectal examinations, the surface of ovary was smooth without large follicles or corpus luteum. (researchsquare.com)
  • Hydrolysis of selected organophosphorus insecticides by two bacteria isolated from flooded soil. (cdc.gov)
  • They release proaggregatory materials (eg, ADP) by the release reaction, and they synthesize thromboxane A 2 from arachidonic acid. (medscape.com)
  • Higher World Health Organization grades of follicular lymphoma correlate with better outcome in two Nordic Lymphoma Group trials of rituximab without chemotherapy. (ki.se)
  • Lu et al ( 14 ) observed an increase in cardiac mitochondrial-dependent apoptotic activity in obese rats, shown by increased levels of Bad and cytochrome c release in hearts, as well as suppressed expression of the anti-apoptotic factor B-cell lymphoma 2 (Bcl-2). (spandidos-publications.com)
  • We find that Oral-Facial-Digital syndrome 1 functions as a class II Nucleation promoting factor to promote Arp2/3 complex-mediated actin branching. (bvsalud.org)
  • The present findings revealed that PTTG1 and PTTG3 are two important genes with high expressions in breast cancer relative to normal breast cells, implying their unique roles in breast cancer progression. (medsci.org)
  • Susceptibility to infections, without concomitant hyper-IgE, reported in 1976, is caused by hypomorphic mutation in the phosphoglucomutase 3 (PGM3) gene. (ki.se)
  • Workplace exposure assessment of BNNT from two manufacturing facilities measured boron concentrations in personal breathing zones from non-detectable to 0.95g/m3 and TEM structure counts of 0.0123 0.0094 structures/cm3, concentrations well below what was found with other engineered high aspect ratio nanomaterials like carbon nanotubes and nanofibers. (cdc.gov)
  • Memory cells travel to the primary follicle, where, after exposure to dendritic cells, they differentiate into centroblasts (immunoglobulin class-switch). (medscape.com)
  • Moreover, in mouse mast cells, the H 4 R has been shown to signal to kinases such as ERK1/2 and AKT as well as phosphatidylinositol 3-kinase γ, leading to the production of interleukin 6 ( Desai and Thurmond, 2011 ). (aspetjournals.org)
  • Label-free SARS-CoV-2 detection and classification using phase imaging with computational specificity. (cdc.gov)
  • Platelets contain two unique types of granules: alpha granules and dense granules. (medscape.com)
  • Once activated, platelets have two major mechanisms to recruit additional platelets to the growing hemostatic plug. (medscape.com)
  • Almost all rights reserved.Inch"Background: To determine how the mechanised house and micro composition influence cells renewal along with angiogenesis, 3 varieties of scaffolds had been examined. (abinhibitors.com)
  • 2. PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan. (medsci.org)
  • 3) T cell deficiencies result usually in combined immunodeficiencies (CIDs), where both T cells and antibody production are defective. (lu.se)
  • At least, the growth of nitroso compounds starts with the expression of gene expression controlled from DNA by two transcription factors called RNA polymerase (RNAP). (hiresomeonetodo.com)
  • Hermansky-Pudlak syndrome was first noted in 1959 by Hermansky and Pudlak, who described 2 unrelated persons with albinism with lifelong bleeding tendencies and peculiar pigmented reticular cells in the bone marrow as well as in biopsy samples of the lymph node and the liver. (medscape.com)
  • Elimination of OFD1 or disruption of OFD1-Arp2/3 interaction drives proliferating, non-transformed cells into quiescence with ciliogenesis by an RB-dependent mechanism, while it leads oncogene-transformed/cancer cells to incomplete cytokinesis and irreversible mitotic catastrophe via actomyosin ring malformation. (bvsalud.org)
  • For patient education information, see the Thyroid Cancer Directory . (medscape.com)
  • Patient education information on thyroid cancer is also available on the American Cancer Society Web site . (medscape.com)
  • In a recent study, researchers compared radiographic imaging of tumors with an assay of ctDNA, cancer antigen 15-3 ( CA 15-3 ), and circulating tumor cells in 30 women with MBC who were receiving systemic therapy. (medscape.com)
  • 2) T cell deficiencies affect the function in killing infected cells or helping other immune cells. (lu.se)
  • Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection. (cdc.gov)
  • However, there is considerable variation in the numbers of isoforms between H. contortus and C. elegans and an absence of AKT-2 and DDL-2 homologs from H. contortus . (biomedcentral.com)
  • Physicians India 36(3):210-212. (cdc.gov)
  • Together, these results suggest that Smaug and Vts1 define a larger class of post-transcriptional regulators that act in part through a common transcript-recognition mechanism. (embl.de)

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