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.
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.
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.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. (From AMA Drug Evaluations Annual, 1992, p1083)
The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.
Antimetabolites that are useful in cancer chemotherapy.
Physiologically inactive substances that can be converted to active enzymes.
A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*40 allele family.
A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
A phosphatidylinositol 3-kinase subclass that includes enzymes formed through the association of a p110gamma catalytic subunit and one of the three regulatory subunits of 84, 87, and 101 kDa in size. This subclass of enzymes is a downstream target of G PROTEIN-COUPLED RECEPTORS.
Exclusive legal rights or privileges applied to inventions, plants, etc.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.

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)

The family of PI3Ks (phosphatidylinositol 3-kinases) was discovered several decades ago, but until now most attention has been given to class I PI3Ks, mainly due to their previously established role in human disorders such as cancer and metabolic diseases. Class II PI3K has therefore been a bit in the shadow of the more intensively studied other families. Nevertheless, the number of reports about class II has started to increase over the past few years and we are now beginning to gain a clearer picture about the role of class II enzymes in different cellular functions and their involvement in human diseases. The fact that class II PI3K generates different second messengers (phosphoinositides) than the other PI3K family members, gives an indication that these enzymes might play a specific role in the regulation of distinct cellular functions. However, there is still a lot to be learned about the molecular mechanism of activation, the cellular function and the physiological and pathological role ...
The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014 ...
Phosphoinositide 3-kinase (PI3K), class II, alpha isoform, catalytic domain; The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases. PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014 ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014 ...
Forschungsschwerpunkte:. - Signaltransduktion in soliden Tumoren. - Translationale Strategien im Bereich gastrointestinaler Tumoren, Biomarkerentwicklung und co-klinische 3D-Organoidkulturen. - Molekulare Regulation und Isoform-spezifische Funktion von Klasse I und II Phosphoinositid 3-Kinasen. - Onkogene Funktion von GTPasen der RAS und RHO Familien. Research interests:. - Signal transduction in solid tumours. - Translational research in GI malignancies, biomarker development, co-clinical 3D organoid cultures. - Molecular regulation and isoform-specific function of class I and II phosphoinositide 3-kinases (PI3Ks). - Oncogenic roles of small GTPases of the RAS and RHO families. ...
Thank you for your interest in spreading the word about Biochemical Society Transactions.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...
FAG Z-567601-K-C3 Bearing is one of our main products. We have the most detailed information about bearing sale, bearing size, bearing price and bearing dimensions. If you want to know their price, size and other information ,can contact us. Z-567601.ZL-K-W209B-C5 bearing Cylindrical Roller Bearings Brand: FAG Bearing Category: Cylindrical Roller Bearings Model: Z-567601.ZL-K-W209B-C5 d: 180 .... ...
Besenhard, J., Han, J-H., Wachtler, M., Möller, K-C., Wagner, M. R., Papst, I., Hofer, F., Park, H-Y., Park, S-Y., Lee, K-Y. & Winter, M., 23 Jun 2004.. Publikation: Konferenzbeitrag › (Altdaten) Vortrag oder Präsentation › Forschung ...
The boy Holy Communion invitations category features a wonderful, unique selection of First Communion invitations for boys. Personalize and order easily. Orders ship fast!
The glutathione S-transferase (GST) were affinity purified in both mice treated with 200 mg kg-1 benzo (a) pyrene once weekly for 8 weeks and control mice. The affinity purified enzymes were isoelectric focused and three zones were selected in each group of mice. GST in the BaP treated mice were focused into zone I (pI 7.5 ), zone II (pI 8.4) and zone III (pI 9.4). In control mice, the zones were zone I (pI 8.4), zone II (pI 9.2 ) and zone III (pI 9.8. The affinity purified and focused enzymes were subjected to SDS-PAGE and assayed for substrate specificities. The SDS-PAGE of the affinity purified GST revealed 3 subunits of molecular radius of approx. 23, 24.5 and 26 kD in control mice and 24, 26.5 and 28 kD in BaP treated mice. The activities of the focused GST towards 1-chloro-2,4-dinitrobenzene (CDNB) were similar in both BaP treated and control mice. Activities of focused enzymes in the BaP treated mice towards 3,4-dichloronitrobenzene (DCNB) and ethacrynic acid (EA) were higher than control ...
Type II phosphatidylinositol (PtdIns) 4-kinases produce PtdIns 4-phosphate, an early key signaling molecule in phosphatidylinositol cycle, which is indispensable for T cell activation. Type II PtdIns 4-kinase alpha and beta have similar biochemical properties. To distinguish these isoforms Epigallocatechin gallate (EGCG) has been evaluated as a specific inhibitor. EGCG is the major active catechin in green tea having anti-inflammatory, antiatherogenic and cancer chemopreventive properties. The precise mechanism of actions and molecular targets of EGCG in early signaling cascades are not well understood. In the present study, we have shown that EGCG inhibits type II PtdIns 4-kinases (alpha and beta isoforms) and PtdIns 3-kinase activity in vitro. EGCG directly bind to both alpha and beta isoforms of type II PtdIns 4-kinases with a Kd of 2.62 mu M and 1.02 mu M, respectively. Type II PtdIns 4-kinase-EGCG complex have different binding pattern at its excited state. Both isoforms showed significant ...
Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within membrane-bound phagosomes. Maturation of apoptotic cell-containing phagosomes leads to formation of phagolysosomes where cell corpses are degraded. The class III phosphatidylinositol 3-kinase (PI3-kinase) VPS-34 coordinates with PIKI-1, a class II PI3-kinase, to produce PtdIns3P on phagosomes, thus promoting phagosome closure and maturation. Here, we identified UBC-13, an E2 ubiquitin-conjugating enzyme that functions in the same pathway with VPS-34 but in parallel to PIKI-1 to regulate PtdIns3P generation on phagosomes. Loss of ubc-13 affects early steps of phagosome maturation, causing accumulation of cell corpses. We found that UBC-13 functions with UEV-1, a noncatalytic E2 variant, and CHN-1, a U-box-containing E3 ubiquitin ligase, to catalyze K63-linked poly-ubiquitination on VPS-34 both in vitro and in Caenorhabditis elegans. Loss of ubc-13, uev-1, or chn-1 disrupts ubiquitin modification of ...
K-C & More Powder supplement recommended to support a healthy circulatory system in horses. Vitamin K is known as a clotting factor. Veterinarian tested and recommended. Apple flavor.Each scoop contains 3,500 mg ascorbic acid (vitamin C) and 40 mg menadione (vitamin K).Directions: 1 scoop daily. 1 oz scoop enclosed. Safe use in pregnant animals o
Recent evidence suggests that concanavalin A modulates tyrosyl phosphorylation and activation of a type II PtdIns 4-kinase in rat splenic lymphocytes. However, the regulatory protein tyrosine kinase(s) remain to be elusive. The present manuscript provides evidence that a type II PtdIns 4-kinase associates with p56(lck) in Con A stimulated rat splenic lymphocytes. In vitro phosphorylation studies suggest that p561(lck) regulates phosphorylation and activation of type II PtdIns 4-kinase. Inhibition of p561(lck) activity in vivo has shown to reduce tyrosyl phosphorylation and activation of PtdIns 4-kinase by Con A. These results suggest that p56(lck) may be the physiological regulator of type II PtdIns 4-kinase ...
Expression of PIK3C2A (PI3K-C2alpha) in esophagus tissue. Antibody staining with HPA037641 and HPA037642 in immunohistochemistry.
Shi L, Lin Y-H, Sierant MC, Zhu F, Cui S, Guan Y, Sartor MA, Tanabe O, Lim K-C, Engel JDouglas. 2014. Developmental transcriptome analysis of human erythropoiesis.. Hum Mol Genet. 23(17):4528-42. ...
The phosphatidylinositol phosphate kinases (PIPkins) are a family of enzymes involved in regulating levels of several functionally important inositol phospholipids within cells. The PIPkin family is subdivided into three on the basis of substrate specificity, each subtype presumably regulating levels of different subsets of the inositol lipids. The physiological function of the type II isoforms, which exhibit a preference for phosphatidylinositol 5-phosphate, a lipid about which very little is known, is particularly poorly understood. In the present study, we demonstrate interaction between, and co-immunoprecipitation of, type IIα PIPkin with the related, but biochemically and immunologically distinct, type I PIPkin isoforms. Type IIα PIPkin interacts with all three known type I PIPkins (α, β and γ), and in each case co-expression of the type I isoform with type IIα results in recruitment of the latter from the cytosol to the plasma membrane of the cell. This change in subcellular ...
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- ...
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 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 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 ...
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). ...
Class II and III PI3Ks are differentiated from the Class I by their structure and function. The distinct feature of Class II ... Class I PI3Ks catalyze the conversion of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) into phosphatidylinositol (3,4,5)- ... Class I, Class II, Class III, and Class IV. The classifications are based on primary structure, regulation, and in vitro lipid ... Class II comprises three catalytic isoforms (C2α, C2β, and C2γ), but, unlike Classes I and III, no regulatory proteins. Class ...
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 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 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 ...
... 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 PX-866 was starting 4 phase II trials for solid tumours. The company gave an update on its phase 2 trials in Jun 2012. ... September 2015). "Phase II study of PX-866 in recurrent glioblastoma". Neuro-Oncology. 17 (9): 1270-4. doi:10.1093/neuonc/ ...
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 ...
All NKG2D ligands are homologous to MHC class I molecules and are divided into two families: MIC and RAET1/ULBP. Human MIC ... viral replication or some viral products activate the ATM and ATR kinases. These kinases initiate the DNA damage response ... "NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural ... In mice, alternative splicing generates two distinct NKG2D isoforms: the long one (NKG2D-L) and the short one (NKG2D-S). NKG2D- ...
... 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- ...
... 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 ...
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 ...
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 ...
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, ...
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 ... Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in ... The consensus sequence of protein kinase C enzymes is similar to that of protein kinase A, since it contains basic amino acids ...
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 ... and Orally Available Class I Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor (GDC- ... 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 ...
The systematic name of this enzyme class is ATP:1D-myo-inositol-1,3,4,6-tetrakisphosphate 5-phosphotransferase. This enzyme is ... Stevenson-Paulik J, Odom AR, York JD (2002). "Molecular and biochemical characterization of two plant inositol polyphosphate 6 ... This enzyme participates in inositol phosphate metabolism and phosphatidylinositol signaling system. Shears SB (1989). "The ... In enzymology, an inositol-tetrakisphosphate 5-kinase (EC 2.7.1.140) is an enzyme that catalyzes the chemical reaction ATP + 1D ...
The systematic name of this enzyme class is ATP:1D-myo-inositol-3,4,5,6-tetrakisphosphate 1-phosphotransferase. Other names in ... This enzyme participates in inositol phosphate metabolism and phosphatidylinositol signaling system. As of late 2007, 3 ... the two substrates of this enzyme are ATP and 1D-myo-inositol 3,4,5,6-tetrakisphosphate, whereas its two products are ADP and ... inositol-trisphosphate 5-kinase, 1D-myo-inositol-trisphosphate 5-kinase, and ATP:1D-myo-inositol-1,3,4-trisphosphate 5- ...
... the two substrates of this enzyme are ATP and 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate, whereas its two products are ADP ... As of late 2007, 6 structures have been solved for this class of enzymes, with PDB accession codes 2A4Z, 2A5U, 2CHW, 2CHX, 2CHZ ... In enzymology, a phosphatidylinositol-4,5-bisphosphate 3-kinase (EC 2.7.1.153) is an enzyme that catalyzes the chemical ... The systematic name of this enzyme class is ATP:1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 3-phosphotransferase. This ...
1996). "Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the ... 1997). "A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase ... Imai T, Kakizaki M, Nishimura M, Yoshie O (Aug 1995). "Molecular analyses of the association of CD4 with two members of the ... 147 (3): 1030-6. PMID 1650385. Clark K.L.; Zeng Z.; Langford A.L.; Bowen S.M.; Todd S.C. (November 2001). "PGRL is a major CD81 ...
NGF binds with at least two classes of receptors: the tropomyosin receptor kinase A (TrkA) and low-affinity NGF receptor (LNGFR ... Crowder RJ, Freeman RS (Apr 1998). "Phosphatidylinositol 3-kinase and Akt protein kinase are necessary and sufficient for the ... A second pathway contributing to cell survival occurs through activation of the mitogen-activated protein kinase (MAPK) kinase ... which in turn causes the autophosphorylation of the tyrosine kinase segment. The tropomyosin receptor kinase A receptor has ...
Phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks, or PI4P5Ks) are a class of enzymes that phosphorylate phosphatidylinositol ... Both Type I and Type II phosphatidylinositol-4-phosphate 5-kinase (PIP5KI) are further classified as PIP5Kα, PIP5Kβ and PIP5Kγ ... September 2010). "Phosphatidylinositol-4-phosphate 5-kinases and phosphatidylinositol 4,5-bisphosphate synthesis in the brain ... November 1999). "Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in ...
Hepatocyte growth factor-regulated tyrosine kinase substrate is an enzyme that in humans is encoded by the HGS gene. HGS (gene ... Bishop N, Horman A, Woodman P (2002). "Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal ... "Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells". EMBO J. 19 (17): 4577-88. doi:10.1093/emboj/ ... Komada M, Masaki R, Yamamoto A, Kitamura N (1997). "Hrs, a tyrosine kinase substrate with a conserved double zinc finger domain ...
These two kinases regulate autophagy through inhibitory phosphorylation of the Unc-51-like kinases ULK1 and ULK2 (mammalian ... The autophagy-inducible Beclin-1 complex[40] contains the proteins p150, Atg14L and the class III phosphatidylinositol 3- ... E. Itakura, C. Kishi, K. Inoue, and N. Mizushima, 'Beclin 1 Forms Two Distinct Phosphatidylinositol 3-Kinase Complexes with ... Once active, VPS34 phosphorylates the lipid phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns(3)P) on ...
These two kinases regulate autophagy through inhibitory phosphorylation of the Unc-51-like kinases ULK1 and ULK2 (mammalian ... The autophagy-inducible Beclin-1 complex[48] contains the proteins p150, Atg14L and the class III phosphatidylinositol 3- ... Once active, VPS34 phosphorylates the lipid phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns(3)P) on ... "Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG". Molecular Biology of the ...
protein serine/threonine kinase activator activity. • receptor ligand activity. Cellular component. • extracellular region. • ... Russell PJ (2009). iGenetics: A Molecular Approach (3rd ed.). Upper Saddle River, N.J.: Pearson Education. p. 533. ISBN 978-0- ... insulin receptor signaling pathway via phosphatidylinositol 3-kinase. • positive regulation of multicellular organism growth. • ... O'Dell SD, Day IN (Jul 1998). "Insulin-like growth factor II (IGF-II)". The International Journal of Biochemistry & Cell ...
Fyn and Lyn kinase. It also activates phosphatidylinositol 3-kinase (PI3K) and AKT signaling pathway and induce expression of ... Currently there are two varieties of IL-15 superagonist available. One combines IL-15 and IL-15Rα-Fc (R&D Systems) in vitro to ... Ahmad A, Ahmad R, Iannello A, Toma E, Morisset R, Sindhu ST (July 2005). "IL-15 and HIV infection: lessons for immunotherapy ... kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) and Syk (spleen tyrosine kinase) ...
protein kinase activator activity. • 1-phosphatidylinositol-4-phosphate 3-kinase activity. • protein serine/threonine kinase ... II/B α. δ. ε. ζ. Pfu. III/C. IV/X β. λ. μ. TDT. V/Y η. ι. κ. RNA-directed DNA polymerase. Reverse transcriptase Telomerase. ... class IA. • plasma membrane. • lamellipodium. • cytoplasm. • membrane. Biological process. • negative regulation of neuron ... kinase activity. • phosphatidylinositol 3-kinase activity. • phosphatidylinositol-3,4-bisphosphate 5-kinase activity. ...
Mauceri D, Cattabeni F, Di Luca M, Gardoni F (May 2004). "Calcium/calmodulin-dependent protein kinase II phosphorylation drives ... For example, GluA1 binds to SAP97 through SAP97's class I PDZ domain,[8] while GluA2 binds to PICK1[9] and GRIP/ABP. Of note, ... permeable AMPA receptors induce phosphorylation of cAMP response element-binding protein through a phosphatidylinositol 3- ... "Long-term potentiation is associated with an increased activity of Ca2+/calmodulin-dependent protein kinase II". J. Biol. Chem ...
... yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III ... C1QBP has been shown to interact with Protein kinase D1,[10] BAT2,[11] PRKCD,[10] PKC alpha[10] and Protein kinase Mζ.[10] ... phosphatidylinositol 3-kinase signaling. • innate immune system. • viral process. • positive regulation of dendritic cell ... protein kinase C binding. • complement component C1q binding. • adrenergic receptor binding. • translation activator activity. ...
negative regulation of protein kinase B signaling. • cell differentiation. • immune system process. • negative regulation of ... positive regulation of phosphatidylinositol 3-kinase signaling. • positive regulation of apoptotic process. • intracellular ... Manavathi B, Kumar R (June 2006). "Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin". ... These proteins belong to the nuclear hormone receptor class of transcription factors that regulate gene transcription. Since it ...
"BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". ... DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator. • positive ... two quartets of cysteine or histidine residues that coordinate two zinc atoms.[30] This motif contains a short anti-parallel ... "Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells". J. Biol. Chem. ...
... and Extracellular signal-regulated kinases (ERK), p38 mitogen-activated protein kinases (p38 Mpk), and cAMP response element- ... These metabolites contain two double bonds and are named series 2 prostanoids, i.e. PGD2, PGE2, PGF2α, PGI2, TXA2 and PGH2. ... Prostaglandin receptors or prostanoid receptors represent a sub-class of cell surface membrane receptors that are regarded as ... and phosphatidylinositol (3,4,5)-trisphosphate secondary messengers; Phospholipase C (PLC) which when activated is responsible ...
positive regulation of kinase activity. • positive regulation of phosphatidylinositol biosynthetic process. • aging. • cellular ... Serotonin receptors were split into two classes by Gaddum and Picarelli when it was discovered that some of the serotonin- ... Lisuride, an antiparkinson dopamine agonist of the ergoline class, that is also a dual 5-HT2A / 5-HT2C agonist[57] and 5-HT2B ... phosphatidylinositol 3-kinase signaling. • nociception. • temperature homeostasis. • viral process. • positive regulation of ...
About two-thirds of the Drosophila brain is dedicated to visual processing.[143] Although the spatial resolution of their ... PLCβ hydrolyzes phosphatidylinositol (4,5)-bisphosphate (PIP2), a phospholipid found in the cell membrane, into soluble ... Calcium binds to proteins such as calmodulin (CaM) and an eye-specific protein kinase C (PKC) known as InaC. These proteins ... a member of the omega class glutathione S-transferases". The Biochemical Journal. 398 (3): 451-60. doi:10.1042/BJ20060424. PMC ...
The kinase then phosphorylates target enzymes, regulating their activities. The two signal pathways are connected together by ... The largest class by far is class A, which accounts for nearly 85% of the GPCR genes. Of class A GPCRs, over half of these are ... Phosphatidylinositol signal pathwayEdit. Main article: IP3/DAG pathway. In the phosphatidylinositol signal pathway, the ... Class A (Rhodopsin-like), Class B (Secretin-like), Class C (Glutamate Receptor-like), Others (Adhesion (33), Frizzled (11), ...
... and MHC class II molecules) that are critical for developing adaptive immune responses. IL receptor-activated bone marrow- ... protein kinase Cs, calmodulin-modulated myosin light chain kinase, RAF/MEK/Mitogen-activated protein kinases, PKC/Ca2+/ ... complexes which releases Gi that then simulates phospholipase C to cleave phosphatidylinositol triphosphate into inositol ... A critical role for protein kinase c". The Journal of Biological Chemistry. 273 (36): 23258-66. doi:10.1074/jbc.273.36.23258. ...
The PTGDR2 gene is located on human chromosome 11 at position q12.2 (i.e. 11q12.2). It consists of two introns and three exons ... It is a member of the class of prostaglandin receptors which bind with and respond to various prostaglandins. DP2 along with ... DAG activates certain protein kinase C enzymes )PKCs) that phosphorylate and thereby regulate target proteins involved in cell ... including simulation of phospholipase C to cleave phosphatidylinositol triphosphate into inositol triphosphate (IP3) and ...
... and the phosphatidylinositol phosphates (PIPs), involved in calcium-mediated activation of protein kinase C;[76] the ... That is, two-carbon fragments are removed sequentially from the carboxyl end of the acid after steps of dehydrogenation, ... Phenolic lipid, a class of natural products composed of long aliphatic chains and phenolic rings that occur in plants, fungi ... nuclear located protein kinase C and cyclic AMP-dependent protein kinase". Frontiers in Bioscience. 13 (13): 1206-26. doi: ...
BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3». ... DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator. • positive ... RNA polymerase II transcription coactivator activity. • RNA polymerase binding. • identical protein binding. ... Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells». J. Biol. Chem. ...
The two pathways are distinct, not only in where they occur, but also in the reactions that occur, and the substrates that are ... The glycerol released by lipase action is phosphorylated by glycerol kinase in the liver (the only tissue in which this ... They are a subclass of eicosanoids and form the prostanoid class of fatty acid derivatives. The prostaglandins are synthesized ... phosphatidylinositol 4,5-bisphosphate (PIP2), by the cell membrane bound enzyme phospholipase C (PLC). An example of a diacyl- ...
They are typically divided among three classes: Type I IFN, Type II IFN, and Type III IFN. IFNs belonging to all three classes ... Antiviral and antiproliferative effects specific to type I IFNs result from p38 MAP kinase signaling. The phosphatidylinositol ... signaling pathway is also regulated by both type I and type II IFNs. PI3K activates P70-S6 Kinase 1, an enzyme that increases ... Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription.[17] ...
... phosphatidylinositol)(PIPs)和蛋白激酶C以鈣來引導的活化有關[63],前列腺素是一種脂肪酸衍生的類二十烷酸,和炎症和免疫有關[64],甾體荷爾蒙包括雌激素、睾酮及皮質醇,調節像生殖、代謝及血壓等機能,像25-羟基胆固醇等氧化膽固 ... nuclear located protein kinase C and cyclic AMP-dependent protein kinase. Frontiers in Bioscience. 2008, 13 (13): 1206-26. PMID ... Advances in Physiology Education. 2007, 31 (1): 5
phosphatidylinositol-mediated signaling. • negative regulation of transcription from RNA polymerase II promoter. • אוטופגיה. • ... regulation of signal transduction by p53 class mediator. • אפופטוזה. • transcription from RNA polymerase II promoter. • ... receptor tyrosine kinase binding. • p53 binding. • קשירת חלבון דומה. • protein heterodimerization activity. • UB. • RNA ... GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding. • TFIID-class transcription factor binding. • ...
Two hemichannels, joined together across a cell membrane comprise a Gap Junction channel.. When two identical hemichannel ... Hamel, W; Magnelli, L; Chiarugi, VP; Israel, MA (June 1996). "Herpes simplex virus thymidine kinase/ganciclovir-mediated ... "The distribution of phosphatidylinositol 4,5-bisphosphate in acinar cells of rat pancreas revealed with the freeze-fracture ... Two lipid mono-layers in each membrane can stain as 3 layers plus one layer from the gap between them, similar to two stacked ...
"Src-family tyrosine kinases in activation of ERK-1 and p85/p110-phosphatidylinositol 3-kinase by G/CCKB receptors". The Journal ... Ito M, Iwata N, Taniguchi T, Murayama T, Chihara K, Matsui T (Oct 1994). "Functional characterization of two cholecystokinin-B/ ... 1-phosphatidylinositol-3-kinase regulator activity. • protein binding. • type B gastrin/cholecystokinin receptor binding. • ... regulation of phosphatidylinositol 3-kinase activity. • G-protein coupled receptor signaling pathway. • phospholipase C- ...
Glenview, IL: Pearson Education, Inc. ISBN 978-0-321-86158-0.. *^ Caldwell HK, Young WS III (2006). "Oxytocin and Vasopressin: ... protein kinase activity. • hormone activity. • cysteine-type endopeptidase inhibitor activity involved in apoptotic process. • ... Phosphatidylinositol/calcium. Pituitary gland, brain. Adrenocorticotropic hormone secretion in response to stress;[23] social ... Angiotensin II stimulates AVP secretion, in keeping with its general pressor and pro-volumic effects on the body.[18] ...
Activation of TAAR1 by MDMA triggers protein kinase A and protein kinase C signaling events which then phosphorylates the ... MDMA is known to be metabolized by two main metabolic pathways: (1) O-demethylenation followed by catechol-O-methyltransferase ... MDMA is in the substituted methylenedioxyphenethylamine and substituted amphetamine classes of chemicals. As a free base, MDMA ... isomers of MDA and MDMA on phosphatidyl inositol turnover in cultured cells expressing 5-HT2A or 5-HT2C receptors". ...
protein kinase binding. • ion channel binding. • signaling receptor activity. Cellular component. • integral component of ... The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. ... phosphatidylinositol phospholipase C activity. • G-protein coupled receptor activity. • amino acid binding. • protein ... orally-active parathyroid hormone-releasing drug in two early studies of healthy volunteers and postmenopausal women". Bone. 64 ...
TFIIIC-class transcription factor binding. • kinase activity. • ATP binding. • RNA polymerase III type 3 promoter DNA binding. ... phosphatidylinositol 3-kinase complex. • membrane. • Mitocondria. • TORC1 complex. • organelle membrane. • macromolecular ... "Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes. ". Infect ... protein serine/threonine kinase activity. • transferase activity. • ribosome binding. • protein binding. • protein kinase ...
As Cruz searches for Una Vida's true identity, he learns profound lessons about the human psyche, the nature of memory - and ... Then, Bazan's laboratory in collaboration with the Stephen Prescott lab showed that neuronal diacylglycerol kinase epsilon is ... In 1980, he and his colleagues described those molecular species of phospholipids in photoreceptors contain two docosahexaenoyl ... stearic acid and diacylglycerol accumulation correlates with the loss of phosphatidylinositol 4,5 bisphosphate in cerebrum 2 ...
positive regulation of MHC class II biosynthetic process. • DNA synthesis involved in DNA repair. • positive regulation of ... mitogen-activated protein kinase binding. • deacetylase activity. • bHLH transcription factor binding. • NAD+ binding. • ... positive regulation of phosphatidylinositol 3-kinase signaling. • negative regulation of oxidative stress-induced intrinsic ... negative regulation of protein kinase B signaling. • cell differentiation. • ovulation from ovarian follicle. • chromatin ...
... class III, type II. GO ID. GO:0034272 Aspect. Cellular Component. Description. A class III phosphatidylinositol 3-kinase ... phosphatidylinositol 3-kinase complex II, PtdIns-3-kinase complex II View GO Annotations in other species in AmiGO ...
We now show that the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta) is activated by the T-cell receptor (TCR) and ... This is the first demonstration that a class II PI3K plays a critical role in T-cell activation. ... We previously showed that nucleoside diphosphate kinase beta (NDPK-B), a mammalian histidine kinase, directly phosphorylates ... The inhibition was due to decreased phosphatidylinositol 3-phosphate [PI(3)P] because dialyzing PI3K-C2beta siRNA-treated T- ...
Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 ... Phase 1 Study of PI3 (Phosphatidylinositol-3)-Kinase Inhibitor Copanlisib With Gemcitabine or Cisplatin Plus Gemcitabine in ... Phase 1 Study of PI3 (Phosphatidylinositol-3)-Kinase Inhibitor Copanlisib With Gemcitabine or Cisplatin Plus Gemcitabine in ... A Phase 1 Study of Copanlisib(Phosphatidylinositol-3 Kinase Inhibitor) in Combination With Gemcitabine (Treatment A) or ...
Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are ... class III, type II Source: GO_Central. *pre-autophagosomal structure Source: GO_Central ... IPR011009. Kinase-like_dom_sf. IPR000403. PI3/4_kinase_cat_dom. IPR036940. PI3/4_kinase_cat_sf. IPR018936. PI3/4_kinase_CS. ... IPR011009. Kinase-like_dom_sf. IPR000403. PI3/4_kinase_cat_dom. IPR036940. PI3/4_kinase_cat_sf. IPR018936. PI3/4_kinase_CS. ...
... class III, type II, 1-phosphatidylinositol-3-kinase activity, autophagosome assembly, autophagy of peroxisome ... phosphatidylinositol 3-kinase complex, class III, type I, phosphatidylinositol 3-kinase complex, ... IPR011009 Kinase-like_dom_sf. IPR000403 PI3/4_kinase_cat_dom. IPR036940 PI3/4_kinase_cat_sf. IPR018936 PI3/4_kinase_CS. ... IPR011009 Kinase-like_dom_sf. IPR000403 PI3/4_kinase_cat_dom. IPR036940 PI3/4_kinase_cat_sf. IPR018936 PI3/4_kinase_CS. ...
Association functional classification system (NYHA) Class II; active coronary artery. disease, myocardial infarction within 6 ... We are a Cancer Social Network, Resource Directory & Education Hub supporting all those affected by cancer. knowcancer.com is ... A Phase 1 Study of BAY80-6946 (Phosphatidylinositol-3 Kinase Inhibitor) in Combination With Gemcitabine (Treatment A) or ... A Phase 1 Study of BAY80-6946 (Phosphatidylinositol-3 Kinase Inhibitor) in Combination With Gemcitabine (Treatment A) or ...
... lipid kinase activity (inferred); phosphatidylinositol binding (inferred); INVOLVED IN macroautophagy (ortholog); ASSOCIATED ... ENCODES a protein that exhibits kinase activity (inferred); ... class 2, beta polypeptide. Orthologs:. Homo sapiens (human) : ... ENCODES a protein that exhibits kinase activity (inferred); lipid kinase activity (inferred); phosphatidylinositol binding ( ... phosphatidylinositol kinase activity IBA. FB:FBgn0015277 more .... 13508589. (PMID:21873635). GO_Central. PMID:21873635. ...
J:46628 Misawa H, et al., Cloning and characterization of a novel class II phosphoinositide 3-kinase containing C2 domain. ... Vertebrate Homology Class 3362. 1 human;1 mouse;1 rat;1 chimpanzee;1 cattle;1 dog;1 chicken;1 zebrafish;1 macaque, rhesus. ... IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain. IPR036940 Phosphatidylinositol 3-/4-kinase, catalytic domain ... PIK3C2G, phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma. Orthology source: HomoloGene, HGNC ...
... phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha), Authors: Dessen P. Published in: Atlas Genet ... class 2, alpha polypeptide. phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha. ... ARM-type_fold C2_dom C2_domain_sf Kinase-like_dom_sf Phox PI3/4_kinase_cat_dom PI3/4_kinase_cat_sf PI3/4_kinase_CS PI3K-C2- ... C2 (PS50004) PI3_4_KINASE_1 (PS00915) PI3_4_KINASE_2 (PS00916) PI3_4_KINASE_3 (PS50290) PI3K_C2 (PS51547) PI3K_RBD (PS51546) ...
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 ...
Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) plays a critical role in the pathogenesis of cancer including ... Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) plays a critical role in the pathogenesis of cancer including ... The differential regulation of class I PI3K genes further divides this class into two subclasses: IA and IB. The class IA PI3K ... Class I PI3K genes control the activity of PI3K/AKT signaling and are often genetically altered in glioblastoma (29). Class II ...
... class I or II); PIP5K, 1-phosphatydylinositol-4-phosphate 5-kinase; PIG-P, phosphatidyl-inositolglycan-peptide; PDK1, 3- ... phosphoinositide-dependent kinase 1; PKB, protein kinase B; HR46, honeybee ortholog of Dmel/HR46; PTEN, phosphatidylinositol-3, ... Two-way selection for pollen hoarding revealed a complex phenotypic, hormonal and genetic architecture affecting division of ... Figure 2. The top panel demonstrates the proboscis extension reflex of a restrained worker honey bee. A droplet of sucrose is ...
Phosphatidylinositol kinases. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance ... class 2, alpha polypeptide , PI3KC2 , PI3K-C2alpha , phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha ... Phosphatidylinositol kinases: phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha. Last modified on 29/01/ ... phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha Rat. -. 1687. 1 q34-q35. Pik3c2a phosphatidylinositol- ...
26 ), phosphatidylinositol 3′-kinase (e.g., LY294002; Ref. 27 ), protein kinase C (staurosporine; Ref. 28 ), cyclin-dependent ... This in vitro assay was performed using a PDK-1 kinase assay kit (Upstate) according to the vendors instructions. This cell- ... This mode of inhibition (i.e., ATP competition) is common among numerous classes of protein or lipid kinase inhibitors that ... Values represent the means of two independent determinations.. Immunoprecipitated p70 S6 kinase (p70S6K) Assay.. ...
Class II Phosphatidylinositol 3-Kinases). ... protein kinase B (Akt) signaling pathway, of which the PI3K-γ ... MATERIALS AND METHODS: Cytotoxicity against two human oral squamous cell carcinoma cell lines and two human normal oral ... Classe II de Fosfatidilinositol 3-Quinases/metabolismo. Sepse/complica es. [Mh] Termos MeSH secund rio:. Animais. ... Classe II de Fosfatidilinositol 3-Quinases/gen tica. Citocinas/sangue. Modelos Animais de Doen as. Regula o para Baixo. ...
The present invention provides compounds of formula (I) which inhibit the activity of PI 3-kinase gamma isoform, which are ... useful for the treatment of diseases mediated by the activation of PI 3-kinase gamma isoform. ... 150000001875 compounds Chemical class 0 abstract claims description 278 * 102000003993 Phosphatidylinositol 3-kinases Human ... 108090000430 Phosphatidylinositol 3-kinases Proteins 0 abstract claims description 50 * 201000010099 diseases Diseases 0 ...
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 ...
2000 A Caenorhabditis elegans type I TGF beta receptor can function in the absence of type II kinase to promote larval ... This includes an AAP-1/AGE-1 phosphatidylinositol 3-kinase (PI 3-kinase) (Morris et al. 1996; Wolkow et al. 2002) and PDK-1, ... Gems, D., A. J. Sutton, M. L. Sundermeyer, P. L. Larson, P. S. Albert et al., 1998 Two pleiotropic classes of daf-2 mutation ... weak class 1), m212 (severe class 1), m579 (weak class 2), and e979 (severe class 2). The pattern of DAF-16∷GFP localization ...
Identification of phosphatidylinositol 4-kinase type II beta as HLA class II-restricted target in graft versus leukemia ... CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-γ. Proc Natl Acad Sci U S A. ... How do CD4(+) T cells detect and eliminate tumor cells that either lack or express MHC class II molecules? Front Immunol. 2014; ... Function and regulation of MHC class II molecules in T-lymphocytes: of mice and men. Hum Immunol. 2004;65(4):282-290.. View ...
The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts ... Phosphatidylinositol-3-Kinase/Akt regulates bleomycin-induced fibroblast proliferation and collagen production.. ... The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts ... NIOSHTIC-2 Publications Search. Search Results. Search for NIOSH Publications:. *Advanced Search ...
A collagen-related peptide regulates phospholipase Cγ2 via phosphatidylinositol 3-kinase in human platelets Biochem J (August, ... Role of class II phosphoinositide 3-kinase in cell signalling M. Falasca; M. Falasca 1 ... M. Falasca, T. Maffucci; Role of class II phosphoinositide 3-kinase in cell signalling. Biochem Soc Trans 1 April 2007; 35 (2 ... such as the members of class II. As a consequence, there is still relatively little understanding of the role of these enzymes ...
P13K class 1 / AKT signaling. PDGFRA. PDGFRB. ERBB2. EGFR. FGFR2. MET. FOXO. ATK. CBL. NF1. NRAS. KRAS. HRAS. RAS. ARAF. BRAF. ... two-thirds there. 50105. view. 20:46, 7 August 2012. AlexanderPico. Periodical save, work in progress. 50104. view. 20:35, 7 ... Ontology Term : protein kinase C (PKC) signaling pathway added !. 50167. view. 21:16, 8 August 2012. AlexanderPico. Ontology ... Ontology Term : phosphatidylinositol 3-kinase class II signaling pathway added !. 50165. view. 21:16, 8 August 2012. ...
P13K class 2 signaling. Protein. PIP3. FGFR1. TSC1. P16. ERRFI1. PTEN. RB1. PIK3C2B. MAP2K1. PDPK1. SPRY2. GRB2. PI(3)P. AKT1. ... two-thirds there. 50105. view. 20:46, 7 August 2012. AlexanderPico. Periodical save, work in progress. 50104. view. 20:35, 7 ... Ontology Term : protein kinase C (PKC) signaling pathway added !. 50167. view. 21:16, 8 August 2012. AlexanderPico. Ontology ... Ontology Term : phosphatidylinositol 3-kinase class II signaling pathway added !. 50165. view. 21:16, 8 August 2012. ...
Reduced IL-4-, lipopolysaccharide-, and IFN-gamma-induced MHC class II expression in mice lacking class II transactivator due ... Downregulation of CIITA function by protein kinase a (PKA)-mediated phosphorylation: mechanism of prostaglandin E, cyclic AMP, ... Inactivation of the antiapoptotic phosphatidylinositol 3-kinase-Akt pathway by the combined treatment of taxol and mitogen- ... Constitutive expression of MHC class II genes in melanoma cell lines results from the transcription of class II transactivator ...
Involvement of class II phosphoinositide 3-kinase α-isoform in antigen-induced degranulation in RBL-2H3 cells. ... Phosphatidylinositol Phosphates/metabolism. *RAW 264.7 Cells. *RNA, Messenger/genetics/metabolism. *RNA, Small Interfering/ ... Involvement of class II phosphoinositide 3-kinase α-isoform in antigen-induced degranulation in RBL-2H3 cells. ... In this study, we present findings that suggest that PI3K-C2α, a member of the class II phosphoinositide 3-kinase (PI3K) ...
Hardie DG, MacKintosh RW: AMP-activated protein kinase-an archetypal protein kinase cascade? Bioessays 14 : 699 -704,1992. ... with an autosomal mode of inheritance in at least two generations and with at least two members with age at onset ,35 years. ... The proportions of families with different weight classes were kept constant in the simulations. A similar approach to assess ... The 1p31.11 region contains several interesting candidate genes for diabetes, including phosphatidylinositol 3-kinase class 2β ...
Two predominant receptor classes are the G-protein-coupled receptor class and the receptor tyrosine kinase class. Extracellular ... Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling. Nature. 390, 1997a 410- ... Ca2+/calmodulin-dependent protein kinase II is stimulated by Wnt and frizzled homologs and promotes ventral cell fates in ... including PKC and Ca2+/calmodulin-dependent protein kinase II (CaMKII; Nadif Kasri et al. 2002; Assefa et al. 2004; Patterson ...
Clinical trial, phase II. Phosphatidylinositol 3-Kinase. Class I, Non-Hodgkins lymphoma. ... Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep ... Type I or II diabetes mellitus with HbA1c , 8.5% or fasting plasma glucose , 160 mg/dL at screening. ... Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or ...
Functional Class Functional class of the sequence domain architecture. * Gene neighbors Overlapping genes and two nearest non- ... PI3-kinase regulatory subunit gamma. PI3-kinase subunit p55-gamma. PI3K regulatory subunit gamma. phosphatidylinositol 3-kinase ... The encoded protein contains two SH2 domains through which it binds activated protein tyrosine kinases to regulate their ... Type II diabetes mellitus, conserved biosystem (from KEGG) Type II diabetes mellitus, conserved biosystemInsulin resistance is ...
Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol. Biol. Cell. 19:5360- ... and should not be confused with the mammalian class I and class II PI3Ks. Most recently there has been an explosion of new ... Molecules involved in the induction of autophagy: Atg proteins, Rab proteins, and the class III PI3 kinase. The source of the ... Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes. Anne Simonsen, Sharon A. Tooze ...
  • We now show that the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta) is activated by the T-cell receptor (TCR) and functions upstream of NDPK-B to activate KCa3.1 channel activity. (ox.ac.uk)
  • The inhibition was due to decreased phosphatidylinositol 3-phosphate [PI(3)P] because dialyzing PI3K-C2beta siRNA-treated T-cells with PI(3)P rescued KCa3.1 channel activity. (ox.ac.uk)
  • This is the first demonstration that a class II PI3K plays a critical role in T-cell activation. (ox.ac.uk)
  • Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) plays a critical role in the pathogenesis of cancer including glioblastoma, the most common and aggressive form of brain cancer. (frontiersin.org)
  • 2. Parkinson GN, Vines D, Driscoll PC, Djordjevic S. (2008) Crystal structures of PI3K-C2alpha PX domain indicate conformational change associated with ligand binding. (guidetopharmacology.org)
  • A key component during sepsis is the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, of which the PI3K-γ isoform is a major regulator in many inflammatory responses. (bireme.br)
  • The present study investigated the role of phosphatidylinositol-3-kinase (PI3K)/Akt in fibrogenesis of human lung fibroblasts and its regulation by reactive oxygen species (ROS). (cdc.gov)
  • Although it is now well established that PI3K (phosphoinositide 3-kinase) is a key enzyme in several intracellular processes, there are still relatively few reports that precisely identify the specific isoforms of PI3K actually involved in such events. (portlandpress.com)
  • RBL-2H3 cells were transfected with shRNA targeting PI3K-C2α.The release was increased significantly by the expression of the siRNA-resistant version of PI3K-C2α.These results indicated that PI3K-C2α and its product PtdIns(3,4)P2 may play roles in the secretory process. (nih.gov)
  • In this study, we present findings that suggest that PI3K-C2α, a member of the class II phosphoinositide 3-kinase (PI3K) subfamily, regulates the process of FcεRI-triggered degranulation. (nih.gov)
  • On the vesicles, the existence of PI3K-C2α and PtdIns(3,4)P2 was observed. (nih.gov)
  • These results indicated that PI3K-C2α and its product PtdIns(3,4)P2 may play roles in the secretory process. (nih.gov)
  • Phosphatidylinositol 3-kinase (PI3K) phosphorylates phosphatidylinositol and similar compounds, which then serve as second messengers in growth signaling pathways. (nih.gov)
  • Autophagic activity has been found to be regulated by PI 3-kinases (PI3K), which phosphorylate phosphatidylinositol (PtdIns) or phosphoinositides (PIs, phosphorylated derivatives of PtdIns) at the 3-position of the inositol ring. (rupress.org)
  • The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. (discoverx.com)
  • The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a critical survival pathway for cell proliferation, apoptosis, autophagy and translation in neoplasms. (mdpi.com)
  • LY294002 is a potent, cell permeable inhibitor of phosphatidylinositol 3-kinase (PI3K) that acts on the ATP binding site of the enzyme [1]. (invivogen.com)
  • PI3K is also known to regulate TLR-mediated inflammatory responses [2, 3]. (invivogen.com)
  • We have used isoform-selective inhibitors of class IA PI3K to dissect further the roles of individual p110 isoforms in insulin signalling. (biochemj.org)
  • A large part of our understanding of how PI3K participates in cell signalling is based on the use of two structurally distinct cell-permeable inhibitors of PI3K, LY294002 [ 3 ] and wortmannin [ 4 ]. (biochemj.org)
  • However, the PI3K lipid kinase family comprises eight enzymes, divided into three classes (I, II and III) based on sequence homology comparisons. (biochemj.org)
  • Class I PI3K is subdivided into two subclasses, class IA and class IB. (biochemj.org)
  • There is only one class IB PI3K (p110γ) and this operates downstream of heterotrimeric GPCRs (G-protein-coupled receptors). (biochemj.org)
  • The direct pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) similarly enhances paclitaxel-induced tumor apoptosis in a dose-dependent manner. (aacrjournals.org)
  • In the PI3K-Akt cascade, PI3K phosphorylates lipids to form second messengers PI (3 ,4 ,5) P 3 and PI (3 ,4) P 2 in response to extracellular stimuli. (aacrjournals.org)
  • their constitutive binding serves to stabilize the p110 protein and inhibit p110-PI3K activity 2 . (nature.com)
  • The binding of p85α to newly formed phosphotyrosine sites on activated receptors, either directly or via adapter proteins, relieves the default inhibition of PI3K and also relocalizes p110-PI3K to the plasma membrane 3 , 4 . (nature.com)
  • p110-PI3K phosphorylates phosphatidylinositol (PI) lipids such as PI4,5P 2 converting it to PI3,4,5P 3 , an important lipid second messenger that recruits PH (pleckstrin homology) domain-containing proteins such as PDK1 (3-phosphoinositide-dependent protein kinase 1) and Akt to the plasma membrane 5 . (nature.com)
  • PTEN (phosphatase and tensin homologue deleted on chromosome 10) counteracts PI3K signaling by dephosphorylating PI3,4,5P 3 back to PI4,5P 2 . (nature.com)
  • Deregulation of the PI3K signaling pathway is observed in many human cancers and occurs most frequently through loss of PTEN phosphatase tumor suppressor function or through somatic activating mutations in the Class IA PI3K, PIK3CA . (pnas.org)
  • In this study, we used a single-vector lentiviral inducible shRNA system to selectively inactivate the three Class IA PI3Ks, PIK3CA , PIK3CB , and PIK3CD , to determine which PI3K isoforms are responsible for driving the abnormal proliferation of PTEN-deficient cancers. (pnas.org)
  • Surprisingly, PIK3CA depletion affected neither PI3K signaling nor cell growth in 3 PTEN-deficient cancer cell lines. (pnas.org)
  • In addition, recent sequencing analyses revealed that one of the Class IA PI3K isoforms, PIK3CA , frequently is activated through somatic mutations in many cancers ( 9 - 14 ). (pnas.org)
  • First-generation pan-PI3K inhibitors target all 3 Class IA isoforms ( 24 , 25 ). (pnas.org)
  • The Company's drug candidate is CUDC-907, an orally-available, small molecule inhibitor of histone deacetylase (HDAC) and phosphatidylinositol-3-kinase (PI3K) enzymes. (americanbankingnews.com)
  • CUDC-907 is an oral, dual inhibitor of Class I and II HDAC, as well as Class I PI3K enzymes. (americanbankingnews.com)
  • 3-Methyladenine is a phosphatidylinositol 3-kinase (PI3k) inhibitor, blocking class I, class II, and class III PI3ks. (peprotech.com)
  • Phosphatidylinositol 3-kinase delta (PI3K δ ) is a critical signaling molecule in B cells and is considered a target for development of therapies against various B cell malignancies. (aspetjournals.org)
  • Phosphatidylinositol 3-kinase (PI3K) belongs to a family of lipid signaling kinases that phosphorylate phosphoinositides at the D3 position of the inositol ring ( Cantley, 2002 ). (aspetjournals.org)
  • The δ isoform of the class 1 PI3K (PI3K δ ) has been shown to be critical for B cell signaling and function ( Fung-Leung, 2011 ). (aspetjournals.org)
  • The present study reveals a dual and specific role of phosphatidylinositol 3-kinase (PI3K) in IL-2R endocytosis. (biologists.org)
  • In summary, our results indicate a key role of class I PI3K in IL-2R endocytosis that creates a link with IL-2 signalling. (biologists.org)
  • We show that cells lacking two Dictyostelium class I phosphatidylinositol (PI) 3′ kinases (PI3K and pi3k1/2 -null cells) or wild-type cells treated with the PI3K inhibitor LY294002 are unable to properly polarize, are very defective in the temporal, spatial, and quantitative regulation of chemoattractant-mediated filamentous (F)-actin polymerization, and chemotax very slowly. (rupress.org)
  • Activation of PI3K produces the membrane-soluble products PI 3,4,5-triphosphate (PI[3,4,5]P 3 ) and PI 3,4-bisphosphate (PI[3,4]P 2 ), resulting in the membrane localization and activation of downstream effectors. (rupress.org)
  • The orally bioavailable bismesylate salt of a potent small-molecule thieno[3,2-d]pyrimidine inhibitor of the class I phosphatidylinositol 3 kinase (PI3K) isoforms p100alpha and p100delta with potential antineoplastic activity. (cancer.gov)
  • Aberrantly triggered PI3K pathway promotes carcinogenesis and tumor angiogenesis [3 10 For instance around 30% of breasts cancers proven activating missense mutations of respectively whereas the regulatory p85 subunit- p85 p55 and PP121 p50 isoforms - are encoded by and genes respectively [26 27 Course IB PI3Ks also contain catalytic p110? (immune-source.com)
  • Course II PI3K enzymes also can be found in 3 isoforms (PI3KC2? (immune-source.com)
  • The central area can be made up of the C2 PI3K-type and PIK helical domains whereas the C-terminus provides the catalytic equipment (PI3K/PI4K kinase domain). (immune-source.com)
  • In course II enzymes nevertheless the central area can be made-up of four domains (PI3K-RBD C2 PI3K-type PIK helical PI3K/PI4K kinase) as well as the C-terminal series made up of the C2 and PX domains. (immune-source.com)
  • also acts as main binding site for clathrin trimers and therefore individually modulating clathrin distribution and function [32 33 Course III catalytic enzyme hVps34 can be seen as a an N-terminal C2 PP121 PI3K-type site a located PIK helical site and a C-terminus PI3K/PI4K kinase site [34]. (immune-source.com)
  • Deregulated signaling via the phosphatidylinositol 3-kinase (PI3K) pathway is common in many types of cancer, but its clinicopathological significance in endometrial cancer remains unclear. (nih.gov)
  • The present study demonstrates the presence of complex signaling pathways that might mask the conventional tumorigenic PTEN-PI3K-AKT-mTOR pathway, and strongly suggests a close association between the extracellular-regulated kinase and PI3K pathways in this tumor type. (nih.gov)
  • This gene encodes the 101 kD regulatory subunit of the class I PI3K gamma complex, which is a dimeric enzyme, consisting of a 110 kD catalytic subunit gamma and a regulatory subunit of either 55, 87 or 101 kD. (genecards.org)
  • Phosphoinositide 3-kinase (PI3K)-δ and endoplasmic reticulum (ER) stress are suggested to be involved in steroid-resistant lung inflammation. (bmj.com)
  • Does phosphoinositide 3-kinase (PI3K)-δ play a crucial role in fungus-induced severe allergic lung inflammation? (bmj.com)
  • The mammalian class III PI3K, hVps34, was identified as a homologue of Vps34, the only PI3K present in yeast [ 3 - 5 ], which plays an important role in the regulation of the endocytic pathway and in autophagy [ 5 ]. (pubmedcentralcanada.ca)
  • It has a lipid substrate specificity restricted to PtdIns and is considered as the major producer of the constitutive pool of PtdIns3 P . It is still unclear whether class III PI3K has a basal activity or if it is also regulated by extracellular stimuli. (pubmedcentralcanada.ca)
  • Which medications in the drug class Antineoplastics, PI3K Delta Inhibitors are used in the treatment of Diffuse Large Cell Lymphoma? (medscape.com)
  • This drug class inhibits one or more of the phosphoinositide 3-kinase enzymes, which are part of the PI3K/AKT/mTOR pathway, an important signalling pathway for many cellular functions such as growth control, metabolism and translation initiation. (medscape.com)
  • Pan class I phosphatidylinositol-3-kinase (PI3K) inhibitor with predominant inhibitory activity against PI3K-alpha and PI3K-delta isoforms expressed in malignant B cells. (medscape.com)
  • Deregulation of the phosphoinositide 3-kinase (PI3K) signaling pathway such as by PTEN loss or PIK3CA mutation occurs frequently in human cancer and contributes to resistance to antitumor therapies. (aacrjournals.org)
  • PF-04691502 is an ATP-competitive PI3K/mTOR dual inhibitor, which potently inhibited recombinant class I PI3K and mTOR in biochemical assays and suppressed transformation of avian fibroblasts mediated by wild-type PI3K γ, δ, or mutant PI3Kα. (aacrjournals.org)
  • Inappropriate PI3K signaling, due to genetic aberration, is one of the most frequent occurrences in human cancer ( 1 , 3 ). (aacrjournals.org)
  • Dual PI3K/mTOR inhibitors may most effectively block the PI3K pathway, overcome feedback loops ( 3 ), and block PI3K-independent mTOR activation. (aacrjournals.org)
  • A number of PI3K-selective and PI3K/mTOR-dual inhibitors have entered clinical trials ( 3 , 11 ). (aacrjournals.org)
  • PIK3C2A is belongs to the phosphoinositide 3-kinase (PI3K) family which play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. (sigmaaldrich.com)
  • In HT-29 cells overexpressing Bcl-2, the formation of the beclin and hVps34 complex, which has class III phosphoinositide 3-kinase (PI3K) activity, was inhibited, as was the colocalization of beclin 1 with PI3P (phosphatidylinositol 3-phosphate), suggesting that Bcl-2 inhibited the PI3K activity of the beclin 1-hVSP34 complex. (sciencemag.org)
  • On the basis of structural similarities and substrate specificity, the PI3K family can be subdivided into three classes termed I, II, and III. (abcam.com)
  • The key regulator of the PI3K/Akt pathway is Akt/PKB, a family of three closely related serine/threonine-protein kinases. (antibodies-online.com)
  • Upon activation by receptor tyrosine kinase PI3K phosphorylates PIP2 to PIP3 which then activates Akt signaling. (antibodies-online.com)
  • Class II PI3K has therefore been a bit in the shadow of the more intensively studied other families. (uzh.ch)
  • The fact that class II PI3K generates different second messengers (phosphoinositides) than the other PI3K family members, gives an indication that these enzymes might play a specific role in the regulation of distinct cellular functions. (uzh.ch)
  • PI3KC2β belongs to class II PI3K and has a substrate specificity directed towards PtdIns and PtdIns(4)P, from which it generates PtdIns(3)P and PtdIns(3,4)P2, respectively. (uzh.ch)
  • The members of the class II phosphoinositide 3-kinase (PI3K) family can be activated by several stimuli, indicating that these enzymes can regulate many intracellular processes. (garvan.org.au)
  • By metabolic labeling, we here identify phosphatidylinositol 3-phosphate as the sole in vivo product of the insulin-dependent activation of PI3K-C2alpha, confirming the emerging role of such a phosphoinositide in signaling. (garvan.org.au)
  • This is the first report showing a membrane targeting-mediated mechanism of activation for PI3K-C2alpha and that a small GTP-binding protein can activate a class II PI3K isoform. (garvan.org.au)
  • These studies have further indicated that E4ORF1 bypasses IRS-1 or -2 signaling yet improves glucose disposal by upregulating the distal insulin signaling pathway that involves phosphatidylinositol 3-kinase (PI3K), AKT, and GLUT4 through Ras activation ( 8 ). (diabetesjournals.org)
  • The growth and survival of acute myeloid leukemia (AML) cells are enhanced by the deregulation of signaling pathways such as phosphoinositide 3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR). (aacrjournals.org)
  • Furthermore, the activity of PI3K/Akt and mTOR is closely related, as mTORC2 activates the oncogenic kinase Akt. (aacrjournals.org)
  • The class IA phosphoinositide 3-kinase (PI3K) is a lipid kinase that is mainly induced following growth factor receptor activation. (aacrjournals.org)
  • Upon PI3K stimulation, the generation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) induces the activating phosphorylation by PDK1 of the oncogenic kinase Akt on Thr 308 . (aacrjournals.org)
  • The PI3K signaling pathway is frequently deregulated in cancer cells, and its constitutive activity strongly contributes to the oncogenic process ( 3 ). (aacrjournals.org)
  • In Aim 2, we will define the mechanisms that underlie the beneficial effects of the PI3K? (elsevier.com)
  • First, we determined whether the class IA phosphatidylinositol 3-kinase (PI3K), p110α, contributes to maturation regulation. (ubc.ca)
  • 3-Methyladenine which stops macroautophagy at the sequestration step in mammalian cells also inhibits the phosphoinositide 3-kinase (PI3K) activity raising the possibility that PI3K signaling controls the macroautophagic pathway (Blommaart, E. F. C., Krause, U., Schellens, J. P. M., Vreeling-Sindelárová, H., and Meijer, A. J. (1997) Eur. (semanticscholar.org)
  • a trimer) to prevent it from binding cellular peptides or peptides from the endogenous pathway (such as those that would be loaded onto class I MHC). (wikipedia.org)
  • An intracellular pathway similar to the cognate mammalian and Drosophila pathways acts downstream of the DAF-2 receptor. (genetics.org)
  • Inactivation of the antiapoptotic phosphatidylinositol 3-kinase-Akt pathway by the combined treatment of taxol and mitogen-activated protein kinase kinase inhibition. (unc.edu)
  • Finally, MAC was found to trigger apoptotic death pathway (based on expression levels of cleaved-caspase 3, Bax/Bcl-2 balance, p53 and p21). (biomedcentral.com)
  • 2006. Class I and III Phosphatidylinositol 3'-Kinase Play Distinct Roles in TLR Signaling Pathway. (invivogen.com)
  • Paclitaxel (Taxol) activates a number of signal transduction pathways that lead to apoptosis.In contrast, paclitaxel also activates cell survival pathways, such as the Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway. (aacrjournals.org)
  • The present study focuses on a clathrin-independent dynamin-dependent pathway used by interleukin 2 receptors (IL-2R), essential players of the immune response. (biologists.org)
  • Ras-related C3 botulinum toxin substrate (Rac1) and its targets, the p21-activated kinases (Pak), are specific regulators of this pathway, acting on cortactin and actin polymerization. (biologists.org)
  • The functional characterization of a key enzyme in the phosphatidylinositol (PI) signaling pathway in the model plant Arabidopsis thaliana is the focus of the research summarised in this thesis. (dymocks.com.au)
  • In turn, p-AKT expression was strongly associated with extracellular-regulated kinase 1/2 expression (P = 0.0031), which is representative of the activated RAS-MAP kinase pathway. (nih.gov)
  • In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits metabolic stress, genomic instability and tumorigenesis. (nature.com)
  • Although each Vav isoform was tyrosine phosphorylated upon activation of representative receptor tyrosine kinases, integrin, and lymphocyte antigen receptors, we found unique aspects of Vav protein coupling in each receptor pathway. (asm.org)
  • Common genetic alterations in human melanomas include loss of the tumor suppressor locus CDKN2a , known as a melanoma susceptibility locus ( 3 ), and acquisition of activating mutations or hyperactivation of the Ras pathway. (aacrjournals.org)
  • In these studies the signaling pathway modulated by class II PI3KC2β was investigated. (uzh.ch)
  • A small-molecule inhibitor of D-cyclin transactivation displays preclinical efficacy in myeloma and leukemia via phosphoinositide 3-kinase pathway", Blood Journal, Hemotology Library, vol. 117, No. 6, dol:10.1182/blood-2010-05-284810, Feb. 10, 2011 (Feb. 10, 2011), 13 pages. (patents.com)
  • The PI 3-kinase signaling pathway is emerging as a promising therapeutic target in a number of human diseases including cancer, inflammation and heart disease. (keystonesymposia.org)
  • Although myotubularin was thought to be a dual-specificity protein phosphatase, recent results indicate that it is primarily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and might be involved in the regulation of phosphatidylinositol 3-kinase (PI 3-kinase) pathway and membrane trafficking. (embl.de)
  • THE Tor kinases are key components of an evolutionarily conserved nutrient-responsive pathway that regulates cell growth and proliferation in eukaryotic organisms. (genetics.org)
  • This enzyme participates in 3 metabolic pathways: inositol phosphate metabolism, phosphatidylinositol signaling system, and regulation of the actin cytoskeleton. (wikipedia.org)
  • Therapies targeting essential survival pathways in glioblastoma [e.g., inhibitors of receptor tyrosine kinases (RTKs) or signaling molecules] have achieved modest, yet encouraging, therapeutic benefits in recurrent glioblastoma ( 11 - 22 ). (frontiersin.org)
  • PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. (discoverx.com)
  • The glycosylated inositol derivatives are found in the outer leaflet of the plasma membrane facing the external medium, whereas the phosphorylated phosphatidylinositols are found on the inner leaflet of the lipid bilayer and play an important role on signaling pathways, modulating vital functions of the parasite. (scielo.br)
  • The roles of cell proliferation and growth factor-induced signaling pathways were investigated as well as the class II MHC assembly machinery and functional capacity. (wiley.com)
  • Energy depletion, amino acid, glucose and serum starvation all activate the ULK1 complex via two main pathways: (i) via AMPK (AMP-activated protein kinase), which activates ULK1 by phosphorylation, and (ii) via the inhibition of the mTOR (mammalian target of rapamycin) complex, which inhibits ULK1 by phosphorylation. (springer.com)
  • Signaling pathways emanating from the endoplasmic reticulum (ER) are involved in apoptosis initiated by stimuli as diverse as ER stress, oncogene expression, death receptor (DR) ligation and oxidative stress, and the BCL-2 family is almost invariably implicated in the regulation of these pathways. (nature.com)
  • This review provides an overview of ER-associated apoptotic and autophagic signaling pathways, with particular emphasis on the BCL-2 family proteins. (nature.com)
  • This finding highlights both an additional connection between apoptotic and autophagic pathways and a novel role for BCL-2 family proteins at the ER. (nature.com)
  • Cells can undergo cell death using at least two pathways: apoptotic cell death involving caspases and autophagic cell death involving lysosomes. (sciencemag.org)
  • In this study, we evaluated the effect of blocking the two Ras downstream pathways phosphatidylinositol-3-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase on melanoma development and regression in the TPRas mouse model. (aacrjournals.org)
  • In conclusion, this study strongly supports the role of the phosphatidylinositol-3-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways in the development and maintenance of Ras-dependent melanomas and supports the notion that specific inhibition of these effectors may represent a very promising avenue for the treatment and prevention of the disease. (aacrjournals.org)
  • GRP1 and cytohesin-1 appear to connect receptor-activated PI 3-kinase signaling pathways with proteins that mediate biological responses such as cell adhesion and membrane trafficking. (sciencemag.org)
  • Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. (semanticscholar.org)
  • 2011) Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer. (guidetopharmacology.org)
  • After demonstration of the efficacy of celecoxib in reducing colorectal polyps in patients with familial adenomatous polyposis (1) , use of this cyclooxygenase (COX)-2 inhibitor in the prevention of epithelial malignancies has been the subject of a series of clinical trials. (aacrjournals.org)
  • A 36-amino-acid region of CIITA is an effective inhibitor of CBP: novel mechanism of gamma interferon-mediated suppression of collagen alpha(2)(I) and other promoters. (unc.edu)
  • The PI3-kinase activity of this protein is sensitive to low nanomolar levels of the inhibitor wortmanin. (genecards.org)
  • 1994. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4- morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). (invivogen.com)
  • Here, we find that the combination of paclitaxel with a MEK inhibitor leads to a dramatic inactivation of the antiapoptotic Akt (protein kinase B) kinase. (aacrjournals.org)
  • The ability of 3-methyladenine to suppress the formation of electron microscopically visible autophagosomes suggests that it may be regarded as a specific inhibitor of autophagy. (peprotech.com)
  • Although the B cell-specific monoclonal anti-CD20 antibody rituximab and small-molecule Bruton's tyrosine kinase inhibitor ibrutinib have significantly improved the prognosis for these patients, the annual mortality rate remains high with 12,000 estimated deaths in 2016. (aspetjournals.org)
  • MTOC reorientation in response to peptide-MHC complexes is sensitive to the phosphatidylinositol 3-kinase inhibitor wortmannin. (jimmunol.org)
  • Thus, Bcl-2 appears to be a more general inhibitor of cell death than previously appreciated. (sciencemag.org)
  • Therefore, LY294002 might be the inhibitor of choice in experiments that involve incubation times longer than 2-3 hours. (biologists.org)
  • We therefore tested the dual phosphoinositide 3-kinase/mTORC1/2 ATP-competitive inhibitor NVP-BEZ235 in AML. (aacrjournals.org)
  • Background Copanlisib is a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α- and δ-isoforms. (semanticscholar.org)
  • pan-phosphatidylinositol 3-kinase inhibitor) plus paclitaxel, with and without bevacizumab or trastuzumab, or in combination with letrozole, in patients with locally recurrent or metastatic breast cancer. (biomedcentral.com)
  • Kinetics of PDK-1 inhibition by celecoxib with respect to ATP suggest that celecoxib derivatives inhibit PDK-1 by competing with ATP for binding, a mechanism reminiscent to that of many kinase inhibitors. (aacrjournals.org)
  • In this study, we carried out structure-based optimization of celecoxib using an integrated approach combining structure-activity analysis and molecular modeling, leading to two potent PDK-1 inhibitors, OSU- 03012 and OSU-03013, with IC 50 values at the low μ m range. (aacrjournals.org)
  • The lack of specific inhibitors has made it particularly difficult to address the physiological roles of some isoforms, such as the members of class II. (portlandpress.com)
  • 1997. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. (invivogen.com)
  • Tumors harboring activated p110α, the protein product of PIK3CA , require p110α activity for growth and survival and hence are expected to be responsive to inhibitors of its lipid kinase activity. (pnas.org)
  • On the other hand, recent successes in developing small-molecule inhibitors against activated kinases have spurred considerable interest in PI3Ks as targets for anticancer drugs ( 21 , 22 ). (pnas.org)
  • ATP-competitive mTOR kinase inhibitors may therefore have greater efficacy than rapamycin analogues by inhibiting both mTORC1 and mTORC2 ( 15, 16 ). (aacrjournals.org)
  • In this study, we compared the effects of SKI-606 with Iressa, Src/Abl and EGF-R kinase inhibitors, respectively, on selected parameters in HeLa and SiHa cervical cancer cell lines, which express E6/E7 oncoproteins of high-risk HPV types 18 and 16, respectively. (hindawi.com)
  • Inhibitors have been very useful for characterizing the functions of PI 3-kinases in mammalian cells. (biologists.org)
  • One of the most exciting developments in this field is the discovery of new PI 3-kinase inhibitors. (keystonesymposia.org)
  • No specific inhibitors of the kinases that generate this phosphoinositide have been described, and the coexistence of multiple kinase isoforms and splice variants has precluded genetic analysis. (rupress.org)
  • extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC class II molecules prior to their migration to the cell surface. (wikipedia.org)
  • Because class II MHC is loaded with extracellular proteins, it is mainly concerned with presentation of extracellular pathogens (for example, bacteria that might be infecting a wound or the blood). (wikipedia.org)
  • The invariant chain also facilitates the export of class II MHC from the ER to the golgi, followed by fusion with a late endosome containing endocytosed, degraded proteins. (wikipedia.org)
  • The nSH2 and cSH2 domains of p85α bind to phosphotyrosine sites on upstream signaling proteins such as activated receptor tyrosine kinases (RTK) 19 . (nature.com)
  • After decades of work, many Ca 2+ /CaM-binding proteins have been identified, including Ca 2+ /CaM-dependent protein kinases and phosphatases, proteins involved in second-messenger generation, and proteins that regulate cytoskeletal elements ( 12 , 13 ). (pnas.org)
  • PIP 3 functions as a second messenger that controls a number of cellular processes, including growth, survival, adhesion, and migration, by serving as a docking site for plasma membrane recruitment of many pleckstrin homology domain-containing proteins, such as protein kinase B/Akt ( Okkenhaug and Vanhaesebroeck, 2003 ). (aspetjournals.org)
  • We demonstrate that in response to chemoattractants three PH domain-containing proteins do not localize to the leading edge in pi3k1/2 -null cells, and the translocation is blocked in wild-type cells by LY294002. (rupress.org)
  • Cells lacking one of these proteins, phdA -null cells, exhibit defects in the level and kinetics of actin polymerization at the leading edge and have chemotaxis phenotypes that are distinct from those described previously for protein kinase B (PKB) ( pkbA )-null cells. (rupress.org)
  • This area provides the binding site for GRB2 (Development factor receptor-bound proteins 2) an adapter proteins that frequently complexes with SOS and Ras-GTPases and facilitates recruitment and activation of PI3KC2? (immune-source.com)
  • Once activated, AKT phosphorylates many target proteins regulating a wide range of cellular functions ( 1, 2 , 9, 10 ). (aacrjournals.org)
  • These two PtdIns3P-binding proteins characterize the third functional module. (springer.com)
  • Bacterial invasion of cells, intracellular survival, and aspects of intercellular spread are mediated by bacterial effector proteins delivered into the cell cytoplasm by the Shigella type 3 secretion system. (prolekare.cz)
  • PIK3C2A contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases that act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. (sigmaaldrich.com)
  • Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. (nature.com)
  • Integrin-induced tyrosine phosphorylation of Vav proteins was not detected in nonhematopoietic cells unless the protein tyrosine kinase Syk was also expressed, suggesting that integrin activation of Vav proteins may be restricted to cell types that express particular tyrosine kinases. (asm.org)
  • Vav proteins are Rho family guanine nucleotide exchange factors that are ideally suited to couple receptors to Rho GTPases because they contain multiple protein domains that can bind to receptors or receptor-associated signaling proteins ( 3 , 35 ). (asm.org)
  • Using a yeast autophagy reconstitution assay and two transfected mammalian cell systems, Bcl-2 was found to inhibit beclin 1-mediated formation of autophagic structures through a mechanism that required the functional binding sites mediating the interaction between these two proteins. (sciencemag.org)
  • The analysis of two tandem mass spectra for each methyl-specific antibody resulted in the identification of over 200 new proteins that are putatively arginine-methylated. (mcponline.org)
  • Another class of dimethylated proteins includes RNA-binding proteins ( 18 , 19 ). (mcponline.org)
  • FYVE, PX and PH domains mediate the binding of effector proteins to the lipid products of PI 3-kinases. (biologists.org)
  • Unlike most organisms that express only one Tor protein, Saccharomyces cerevisiae has two highly homologous Tor proteins, Tor1 and Tor2, which are thought to share all of the rapamycin-sensitive functions attributable to Tor signaling, while only Tor2 serves a unique and essential rapamycin-insensitive role (reviewed in C respo and H all 2002 ). (genetics.org)
  • The Tor proteins form two distinct multiprotein complexes: TORC1 and TORC2. (genetics.org)
  • To understand why yeast cells express two functional Tor proteins, we sought to define novel Tor1- or Tor2-specific functions. (genetics.org)
  • These include p110 isoforms regulated by p85 subunits containing SRC homology 2 (SH2) domains ( 3 ), a p110γ PI 3-kinase regulated by heterotrimeric guanine nucleotide-binding proteins ( 4 ), and a PI 3-kinase containing a homology domain (C2 domain) thought to bind membrane lipids ( 5 ). (sciencemag.org)
  • BBB damage will be assessed by the spatial and tem poral analysis of key BBB proteins and potential correlation with changes in activation/expression of NF-?B, CD147, MMP-9 and/or MMP-3 on cerebral vessels. (elsevier.com)
  • Four proteins able to disrupt yeast VPS were identified in this screen, two hypothetical proteins, Rv0900 and Rv1268c, the P-type ATPase Rv0425c, and PE-PGRS62. (ubc.ca)
  • ERK phosphorylates additional kinases and specific transcription factors important in cell proliferation and survival. (aacrjournals.org)
  • Initiation of this signaling cascade commences with the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) to produce phosphatidylinositol 3,4,5-triphosphate (PIP3), which results in cell proliferation, motility, and survival, among many other cellular changes ( 1 ). (pnas.org)
  • Both MAPK/ERK-1/2 and phosphatidylinositol 3-kinase/Akt controlled cell proliferation and HLA-DR expression, but only MAPK/ERK-1/2 controlled the induction of the class II MHC transcription activator protein CIITA, the major determinant of HLA-DR transcription. (wiley.com)
  • In addition to class II molecules bearing the appropriate peptide, adhesive and costimulatory interactions are required to induce T cell proliferation and effector function ( 1 , 2 , 3 ). (jimmunol.org)
  • OspB induces increased cell proliferation by activating mTORC1 kinase, a master regulator of cellular growth, in a manner that depends on IQGAP1. (prolekare.cz)
  • T cells lacking Vav1 are impaired in antigen-induced cell proliferation, activation of NFAT and NFκB, interleukin-2 (IL-2) production, and clustering of actin with the T-cell receptor (TCR) into patches and caps ( 7 , 12 , 13 , 20 , 41 , 54 ). (asm.org)
  • The blockade of Akt activation through the inhibition of 3-phosphoinositide-dependent kinase-1 (PDK-1) represents a major signaling mechanism whereby celecoxib mediates apoptosis. (aacrjournals.org)
  • Docking of potent compounds into the ATP-binding site of PDK-1 was performed for lead optimization, leading to two compounds, OSU-03012 and OSU-03013, with IC 50 values in PDK-1 inhibition and apoptosis induction in the low μ m range. (aacrjournals.org)
  • Exposure of PC-3 cells to these agents led to Akt dephosphorylation and inhibition of p70 S6 kinase activity. (aacrjournals.org)
  • Screening in a panel of 60 cell lines and more extensive testing in PC-3 cells indicated that the mean concentration for total growth inhibition was ∼3 μ m for both agents. (aacrjournals.org)
  • Downregulation of CIITA function by protein kinase a (PKA)-mediated phosphorylation: mechanism of prostaglandin E, cyclic AMP, and PKA inhibition of class II major histocompatibility complex expression in monocytic lines. (unc.edu)
  • The inhibition of these two signaling cascades by topically applied Ly294002 and U0126 significantly delayed melanoma development and significantly decreased the tumor incidence, particularly when the drugs were applied in combination. (aacrjournals.org)
  • We therefore suggest that opening of the tight junctions and inhibition of Na + /H + exchange caused by PtdIns(4,5)P 2 hydrolysis combine to account, at least in part, for the fluid loss observed during Salmonella -induced diarrhea. (rupress.org)
  • Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma. (semanticscholar.org)
  • Even though Class IA isoforms share many structural and regulatory similarities, the increasing biological understanding of these lipid kinases indicates that they have nonredundant cellular functions ( 26 - 29 ). (pnas.org)
  • Class I PI3Ks, which include four isoforms ( α , β , γ , and δ ), are dual-specificity lipid and protein kinases that catalyze the phosphorylation of phosphatidylinositol-4,5-bisphophate, giving rise to phosphatidylinositol-3,4,5-triphosphate (PIP 3 ). (aspetjournals.org)
  • Multiple alternatively spliced transcript variants encoding two distinct isoforms have been found. (genecards.org)
  • However, it is not known whether the recently identified isoforms Vav2 and Vav3, which are broadly expressed, can couple with similar classes of receptors, nor is it known whether all Vav isoforms possess identical functional activities. (asm.org)
  • Mouse models which target individual PI 3-kinase isoforms have shed light on the roles of these enzymes in immune cell function, mast cell degranulation and leukocyte migration. (keystonesymposia.org)
  • Hydrolysis of PtdIns(4,5)P 2 by phospholipase C yields diacylglycerol, a potent activator of most protein kinase C isoforms and other enzymes bearing C1 domains, and inositol 1,4,5-trisphosphate, which induces release of calcium stored in the endoplasmic reticulum ( Taylor, 2002 ). (rupress.org)
  • These include certain protein kinase C isoforms ( 13 ) and the pleckstrin homology (PH) domain-containing protein kinases c-Akt and Btk ( 14 ). (sciencemag.org)
  • Recent genetic knock-in and pharmacological approaches have suggested that, of class IA PI3Ks (phosphatidylinositol 3-kinases), it is the p110α isoform (PIK3CA) that plays the predominant role in insulin signalling. (biochemj.org)
  • PI3Ks (phosphatidylinositol 3-kinases) catalyse the phosphorylation of the D-3 position of the inositol headgroup of PI (phosphatidylinositol) leading to the synthesis of second messengers PtdIns3 P , PtdIns(3,4) P 2 , PtdIns(3,5) P 2 and PtdIns(3,4,5) P 3 [ 1 , 2 ]. (biochemj.org)
  • Class IA PI3Ks are heterodimers consisting of a catalytic subunit (p110) and a regulatory subunit. (biochemj.org)
  • Cellular phosphatidylinositol 3,4,5-triphosphate levels are regulated tightly by the opposing activities of the lipid phosphatase PTEN and the lipid kinase activity of Class IA PI3Ks ( 2 ). (pnas.org)
  • Of particular interest are the Class IA PI3Ks, which encompass the three p110 lipid kinase subunits, p110α, p110β, and p110δ, because they are primarily responsible for phosphorylating the critical signaling molecule, PIP 2 ( 23 ). (pnas.org)
  • PI3Ks are divided into three classes (class I, II, and III) according to their structure, regulation, and substrate specificity. (aspetjournals.org)
  • Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that regulate diverse cellular procedures including PP121 proliferation adhesion success and motility. (immune-source.com)
  • Intro Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that play central part in rules of cell routine apoptosis DNA restoration senescence angiogenesis mobile rate of metabolism and motility [1]. (immune-source.com)
  • The N-termini of class II PI3Ks are more related distantly. (immune-source.com)
  • Phosphatidylinositol 3-kinases (PI3Ks) phosphorylate the inositol ring of phosphatidylinositol at the 3-prime position, and play important roles in cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. (genecards.org)
  • The PI3Ks are divided into three classes: I, II and III, and only the class I PI3Ks are involved in oncogenesis. (genecards.org)
  • This lipid can be produced by the class III and possibly by class II PI3Ks (phosphoinositide 3-kinases) [ 3 ]. (pubmedcentralcanada.ca)
  • Following their activation by receptor tyrosine kinases (RTK), class IA PI3Ks phosphorylate phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3), which recruits AKT, and PDK1 to the plasma membrane ( 6 ). (aacrjournals.org)
  • Phosphoinositide 3-kinases (PI3Ks) phosphorylate phosphatidylinositols (PIs) at their 3´ OH position generating lipid second messengers and thereby regulate numerous biological processes including cell growth, differentiation, survival, proliferation, migration and metabolism. (abcam.com)
  • The class I members can be further subdivided into class IA and IB PI3Ks. (abcam.com)
  • PI3Ks are an enzyme family that phosphorylate PtdIns (Phosphatidylinositol) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). (antibodies-online.com)
  • The family of PI3Ks (phosphatidylinositol 3-kinases) was discovered several decades ago, but until now most attention has been given to class I PI3Ks, mainly due to their previously established role in human disorders such as cancer and metabolic diseases. (uzh.ch)
  • However, there is still a lot to be learned about the molecular mechanism of activation, the cellular function and the physiological and pathological role of class II PI3Ks. (uzh.ch)
  • The activation of class II PI3Ks is not completely defined yet, but it is known that they do not bind to any regulatory subunits. (uzh.ch)
  • Although we find that p110α is necessary for insulin-stimulated phosphorylation of PKB (protein kinase B) in several cell lines, we find that this is not the case in HepG2 hepatoma cells. (biochemj.org)
  • OspB has been shown previously to modulate NF-κB activation and phosphorylation of ERK1/2 and activation of cytosolic phospholipase A 2 and associated IL-8 secretion and transepithelial polymorphonuclear leukocyte migration [ 14 - 16 ]. (prolekare.cz)
  • In addition, the best-characterized Vav protein, Vav1, is activated by two common signals generated by multiple classes of plasma membrane receptors: tyrosine phosphorylation and the phosphatidylinositol (PI) 3′-kinase product, PI-3,4,5-P 3 ( 3 , 16 ). (asm.org)
  • Stimulation of diverse cell surface receptors including immune response receptors, integrins, and growth factor receptors leads to tyrosine phosphorylation of Vav1 ( 3 , 6 , 14 , 31 , 55 ). (asm.org)
  • The p85-p110 and p110γ type PI 3-kinases that are specifically activated by receptor signaling systems exhibit broad substrate specificities, and their activation leads to rapid phosphorylation of the inositol D-3 positions on PtdIns, PtdIns-4-phosphate [PtdIns(4)P], and PtdIns-4,5-bisphosphate [PtdIns(4,5)P 2 ] ( 6 ). (sciencemag.org)
  • Two predominant receptor classes are the G-protein-coupled receptor class and the receptor tyrosine kinase class. (royalsocietypublishing.org)
  • Most gastrointestinal stromal tumors (GISTs) arise due to gain-of-function mutations of KIT and PDGFRA , encoding the receptor tyrosine kinase (RTK). (mdpi.com)
  • In humans, the MHC class II protein complex is encoded by the human leukocyte antigen gene complex (HLA). (wikipedia.org)
  • HLAs corresponding to MHC class II are HLA-DP, HLA-DM, HLA-DOA, HLA-DOB, HLA-DQ, and HLA-DR. Mutations in the HLA gene complex can lead to bare lymphocyte syndrome (BLS), which is a type of MHC class II deficiency. (wikipedia.org)
  • However, complex differences among daf-2 alleles complicate analysis of this gene. (genetics.org)
  • Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and kinase activity . (genecards.org)
  • A cell cycle-coordinated Polymerase II transcription compartment encompasses gene expression before global genome activation. (abcam.com)
  • Such an increase in the gene expression after axotomy was observed in a similar time course for PI3 kinase and skin type-fatty acid binding protein (FABP), suggesting a functional relation between PI-signal and FABP.Thus the gene knockout for s-FABP is under way in co-operation with Dr.F.Spener. (nii.ac.jp)
  • PIK3R5 (Phosphoinositide-3-Kinase Regulatory Subunit 5) is a Protein Coding gene. (genecards.org)
  • Gene Ontology (GO) annotations related to this gene include G-protein beta/gamma-subunit complex binding and 1-phosphatidylinositol-3-kinase regulator activity . (genecards.org)
  • The protein encoded by this gene associates with class II major histocompatibility complex (MHC) and is an important chaperone that regulates antigen presentation for immune response. (cancerindex.org)
  • A key class of signaling molecules that mediate receptor-induced rearrangements of the actin cytoskeleton, activation of kinase cascades, and changes in gene transcription is the Rho family of GTPases ( 46 ). (asm.org)
  • The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. (antibodies-online.com)
  • This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. (antibodies-online.com)
  • Structural organization of the mouse phosphatidylinositol 3-kinase p110d gene. (embl.de)
  • In yeast the Vps34 gene product, a PI 3-kinase with substrate specificity restricted to phosphatidylinositol (PtdIns), is required for correct sorting of carboxypeptidase Y to the vacuole ( 1 ). (sciencemag.org)
  • At the same time, DAG produced by PIP 2 hydrolysis can act as an additional second messenger to further activate downstream targets such as protein kinase C (PKC). (royalsocietypublishing.org)
  • Recent studies have provided significant insights into the roles of PI 3-kinases, their catalytic products and their downstream effectors in membrane trafficking. (biologists.org)
  • PI3KC2β is activated downstream of receptor tyrosine kinases (RTKs) and G protein-coupled receptors upon stimulation by growth factors such as epidermal growth factor, stem cell factor and phospholipids, including LPA (lysophosphatic acid). (uzh.ch)
  • As described here, microscopic analysis of null mutants have revealed that the class I phosphoinositide 3-kinases, PIK1 and PIK2, and the downstream effector protein kinase B (PKB/Akt) are important in regulating completion of macropinocytosis. (embl.de)
  • The DAF-2 insulin/IGF-1 receptor regulates development, metabolism, and aging in the nematode Caenorhabditis elegans . (genetics.org)
  • Phosphatidylinositol-3-Kinase/Akt regulates bleomycin-induced fibroblast proliferation and collagen production. (cdc.gov)
  • Cdk9 regulates a promoter-proximal checkpoint to modulate RNA polymerase II elongation rate in fission yeast. (abcam.com)
  • It has been shown that arginine methylation regulates protein localization ( 2 ). (mcponline.org)
  • The PH domain of the closely related protein cytohesin-1, which, through its Sec7 homology domain, regulates integrin β2 and catalyzes guanine nucleotide exchange of the small guanine nucleotide-binding protein ARF1, was also found to specifically bind PtdIns(3,4,5)P 3 . (sciencemag.org)
  • Additionally, 3-phosphoinositides appear to bind certain SH2 domains, including those within the p85 regulatory subunit of p110 PI 3-kinase ( 16 ). (sciencemag.org)
  • To identify general receptors for phosphoinositides (GRPs), we developed an expression library screening procedure using bovine brain phospholipids labeled with [γ- 32 P]adenosine triphosphate (ATP) in the presence of the glutathione-S-transferase (GST) fusion protein GST-p110 PI 3-kinase ( 18 ). (sciencemag.org)
  • Filters were incubated with mixed brain phosphoinositides labeled at the 3′ position with p110 PI 3-kinase and [γ- 32 P]ATP, and then washed. (sciencemag.org)
  • Phagosomes from p110α knockdown cells were markedly deficient in LAMP-1, LAMP-2 and β-galactosidase, and could not fuse with lysosomes. (ubc.ca)
  • At the cellular level, celecoxib inhibits COX-2 and causes cell cycle arrest and apoptosis in cancer cells. (aacrjournals.org)
  • Furthermore, rapamycin analogues cannot inhibit mTORC2, an AKT upstream kinase ( 3 , 11 , 13 ), although prolonged exposure inhibits mTORC2 assembly in some cell types ( 14 ). (aacrjournals.org)
  • now show that Bcl-2 also inhibits autophagy through its interactions with beclin 1. (sciencemag.org)
  • Overexpression of a rat kinase-deficient phosphoinositide 3-kinase, Vps34p, inhibits cathepsin D maturation. (embl.de)
  • ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate. (uniprot.org)
  • 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)
  • PI 3-Kinases (phosphoinositide 3-kinases, PI 3-Ks) are a family of lipid kinases capable of phosphorylating the 3'OH of the inositol ring of phosphoinositides. (genecards.org)
  • 1999). Its action rests in the formation of a complex set of inositol-containing lipids, whose parent compound is the phospholipid phosphatidylinositol (PI), which can be further phosphorylated or glycosylated forming new classes of bioactive molecules, as depicted in Figure 1 . (scielo.br)
  • Moreover, a particular focus is the exploration of the biological functions of Arabidopsis phophatidylinositol monophosphate 5-kinase 2 (PIP5K2) which catalyzes the synthesis of phophatidylinositol (4,5) bisphosphate, the precursor of two important second messengers (inositol 1,4,5-trisphosphate and diacylglycerol). (dymocks.com.au)
  • PI 3-kinases phosphorylate PtdIns or PIs at the 3-position of the inositol ring ( Fig. 1 ). (biologists.org)
  • Here we discuss the cross talk between autophagy and intracellular compartments, highlighting recent exciting data about the role and regulation of the Vps34 class III phosphatidylinositol (PI) 3-kinase in autophagy. (rupress.org)
  • Regulation of expression and trafficking of perforin-2 by LPS and TNF-α. (invivogen.com)
  • Previous reports showed that suppression of nuclear factor-κB, activation of AMPK/SIRT1, modulation of cyclooxygenase (COX) activity, and up-regulation of novel anti-inflammatory lipid mediators such as protectins, maresins, and resolvins, are the main mechanisms of antineoplastic effect of omega-3 FAs. (springer.com)
  • 2. presynaptic autoreceptors for NE regulation (ie. (brainscape.com)
  • Uncoupling Rac-mediated protrusion and polarization suggests a paradigm of two-tiered PI(3)K-mediated regulation of cell motility. (nih.gov)
  • The mammalian target of rapamycin (mTOR) kinase is implicated in the regulation of initiation of mRNA translation, cell cycle progression, and cellular proliferation. (aacrjournals.org)
  • This down-regulation was not caused through effects on synthesis or stability of Drosha and Dicer, two essential enzymes involved in miRNA maturation. (ubc.ca)
  • nearly 100% of glioblastoma patients will succumb to tumor recurrence if they live more than 2 years. (frontiersin.org)
  • Tumor assessments will be done at Screening, every 8 weeks during Year 1, every 12 weeks during Year 2, and every 6 months during Year 3. (clinicaltrials.gov)
  • Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. (medscape.com)
  • Autophagy is involved in the adaptation to starvation, in cell differentiation and development, as well as in the degradation of aberrant structures, the turnover of organelles, tumor suppression, innate and adaptive immunity, life span extension, and cell death [ 2 , 3 ]. (springer.com)
  • PIK3C2A can phosphorylate phosphatidylinositol and phosphatidylinositol-4-phosphate in vitro. (sigmaaldrich.com)
  • 110 kDa) and a non-catalytic subunit (MW 50, 55, 85, or 101 kDa) and are known to phosphorylate phosphatidylinositol (PI), phosphatidylinositol-4-mono-phosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2) in vitro. (abcam.com)
  • During synthesis of class II MHC in the endoplasmic reticulum, the α and β chains are produced and complexed with a special polypeptide known as the invariant chain. (wikipedia.org)
  • Depletion of PtdIns(4,5)P 2 in intact SigD-injected cells was verified by detachment from the membrane of the pleckstrin homology domain of phospholipase Cδ, used as a probe for the phosphoinositide by conjugation to green fluorescent protein. (rupress.org)
  • The phosphatidylinositol (PI) cycle is activated in response to many hormones and growth factors that bind to cell surface receptors. (royalsocietypublishing.org)
  • IP 3 subsequently binds to receptors (IP 3 R) located principally on the ER triggering the rapid release of Ca 2+ into the cytosol of the cell. (royalsocietypublishing.org)
  • These morphological changes are accompanied by the recruitment to the cell:cell interface of a number of cell surface receptors such as the TCR, CD4, and the integrin LFA-1, as well as signaling molecules such as protein kinase Cθ ( 13 , 14 , 15 , 16 ). (jimmunol.org)
  • Where do we see alpha 2 receptors? (brainscape.com)
  • What are some effects of stim of alpha 2 receptors? (brainscape.com)
  • Where are Beta-2 adrendergic receptors? (brainscape.com)
  • What are the effects of stim of beta-2 adrenergic receptors? (brainscape.com)
  • Where are beta 3 adrenergic receptors? (brainscape.com)
  • What are the key second messengers of alpha-2 receptors? (brainscape.com)
  • Whereas subclass IA PI 3-kinases are typically activated by receptor tyrosine kinases (RTKs) or receptors for immunoglobulin G (FcγRs), subclass IB enzymes are activated by G-protein-coupled receptors (GPCRs). (biologists.org)
  • Signal transmission by many cell surface receptors results in the activation of phosphoinositide (PI) 3-kinases that phosphorylate the 3′ position of polyphosphoinositides. (sciencemag.org)
  • Signaling by these 3-polyphosphoinositides appears to regulate such diverse cellular responses as membrane ruffling ( 7 ), chemotaxis ( 8 ), secretory responses ( 9 ), insulin-mediated membrane translocation of glucose transporters ( 10 ), membrane trafficking of growth factor receptors ( 11 ), and regulated cell adhesion ( 12 ). (sciencemag.org)
  • Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) has long been recognized as an important source of second messengers. (rupress.org)
  • These two complexes (modules) are involved in the initiation of autophagy. (springer.com)
  • 73 Myopathy, X-linked, with excessive autophagy: A muscle disorder characterized by childhood early onset of a slowly progressive proximal limb muscle weakness (especially in legs) and elevation of serum creatine kinase, without evidence of cardiac, respiratory or central nervous system involvement. (malacards.org)
  • Class I PI 3-kinases also function to inhibit autophagy. (biologists.org)
  • By contrast, class III PI 3-kinases mainly mediate receptor-independent trafficking events, which mostly are related to endocytic membrane traffic, phagosome maturation and autophagy. (biologists.org)
  • In addition to turnover of cellular components, autophagy is involved in development, differentiation, and tissue remodeling in various organisms ( 2 ). (sciencemag.org)
  • Five functional modules have been defined: The first module is the ULK1 complex (ULK1 is the mammalian homolog of yeast Atg1), the second module is the phosphatidylinositol 3-kinase (PIK3) complex I (which contains PIK3C3/Vps34), and Beclin 1 (Beclin 1 or BECN1 being the mammalian homolog of the yeast Atg6). (springer.com)
  • In mammalian cells three classes of PI 3-kinases have been identified in addition to a Vps34 homolog ( 2 ). (sciencemag.org)
  • This enzyme molecule preferred 1-stearoyl- 2-arachidonoyl phosphatidate as a substrate and its activity was strongly inhibited by phosphatidylinositol (PtdIns) 4,5-bisphosphate. (nii.ac.jp)
  • Bovine PI 3-Kinase alpha differs from the Human enzyme in only 2 positions, K532R and S535C. (abcam.com)
  • As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes 1BO1 and 2GK9. (wikipedia.org)
  • The two major enzymes PRMT1 (type I) and PRMT5 (type II) preferentially methylate arginines located in RG-rich clusters. (mcponline.org)
  • type I enzymes promote the formation of asymmetrical ω- N G , N G -dimethylated arginines (aDMA), 1 and type II enzymes catalyze the formation of symmetrical ω- N G , N ′ G -dimethylated arginines (sDMA) ( 1 ). (mcponline.org)
  • Class II PI 3-kinases are thought to use PtdIns as their in vivo substrate, yielding phosphatidylinositol 3-phosphate [PtdIns(3) P ]. Some evidence has been presented that class II enzymes, similarly to class I PI 3-kinases, can be activated by external stimuli. (biologists.org)
  • Like class II PI 3-kinases, the class III enzymes use PtdIns as a substrate and thus produce PtdIns(3) P . The class III PI 3-kinases are the only ones conserved from lower eukaryotes to plants and mammals, and represent the most ancient form of PI 3-kinases. (biologists.org)
  • Nevertheless, the number of reports about class II has started to increase over the past few years and we are now beginning to gain a clearer picture about the role of class II enzymes in different cellular functions and their involvement in human diseases. (uzh.ch)
  • Mutant sequence analysis (including 11 newly sequenced alleles) reveals that class 1 mutant lesions lie only in certain extracellular regions of the receptor, while class 2 (pleiotropic) and nonconditional missense mutants have lesions only in the ligand-binding pocket of the receptor ectodomain or the tyrosine kinase domain. (genetics.org)
  • Moreover, the MAP kinase family members JNK, ERK, and p38 are also activated in response to a wide variety of extracellular stimuli. (aacrjournals.org)
  • This essential function of PIK3CB in PTEN-deficient cancer cells required its lipid kinase activity. (pnas.org)
  • After MHC class II complexes are synthesized and presented on APCs they are unable to be expressed on the cell surface indefinitely, due to the internalization of the plasma membrane by the APCs. (wikipedia.org)
  • CD28 coengagement overcomes this sensitivity, as does activation via Ab cross-linking of the TCR or via covalent peptide-MHC complexes, suggesting that phosphatidylinositol 3-kinase is not required per se but rather plays a role in signal amplification. (jimmunol.org)
  • The junctional complexes surrounding the injected cells gradually opened and the PtdIns(4,5)P 2 -depleted cells eventually detached from the monolayer, which underwent rapid restitution. (rupress.org)
  • The mTOR serine/threonine kinase belongs to two separate complexes: mTORC1 and mTORC2. (aacrjournals.org)
  • Assortment of phosphatidylinositol 3-kinase complexes--Atg14p directs association of complex I to the pre-autophagosomal structure in Saccharomyces cerevisiae. (semanticscholar.org)
  • Activated PLC converts membrane-bound phosphatidylinositol (4,5)-bisphosphate (PIP 2 ) into IP 3 and lipophilic diacylglycerol (DAG). (royalsocietypublishing.org)
  • Osteoarthritis-associated basic calcium phosphate crystals activate membrane proximal kinases in human innate immune cells. (invivogen.com)
  • Phosphoinositides are considered as highly dynamic players in the spatial and temporal organization of signalling networks that regulate many important cellular processes, including cytoskeleton organization, membrane trafficking or cell survival and proliferation [ 1 , 2 ]. (pubmedcentralcanada.ca)
  • The last functional module consists of the two ubiquitin-like conjugation systems: ATG12-ATG5 and the LC3-phosphatidylethanolamine (PE) (LC3 being the mammalian homolog of yeast Atg8), which are involved in the elongation and closure of the autophagosomal membrane [ 15 , 16 ]. (springer.com)
  • Christie DA, Kirchhof MG, Vardhana S, Dustin ML, Madrenas J. Mitochondrial and plasma membrane pools of stomatin-like protein 2 coalesce at the immunological synapse during T cell activation . (nyu.edu)
  • Localized Rac activation rescued membrane protrusion but not anteroposterior polarization of F-actin dynamics of PI(3)K-inhibited cells. (nih.gov)
  • Phosphoinositide (PI) 3-kinases control essential cellular functions such as cytoskeletal dynamics, signal transduction and membrane trafficking. (biologists.org)
  • Phosphoinositides (PIs), which are phosphorylated derivatives of phosphatidylinositol (PtdIns), are essential in eukaryotic cells, regulating nuclear processes, cytoskeletal dynamics, signalling and membrane trafficking. (biologists.org)
  • In this Commentary, we highlight the functions of PI 3-kinases in membrane trafficking. (biologists.org)
  • Lipid kinases and their phosphorylated products are important regulators of many cellular processes, including intracellular membrane traffic. (embl.de)
  • Depletion of PtdIns(4,5)P 2 was associated with marked alterations in the actin cytoskeleton and its association with the plasma membrane. (rupress.org)
  • In contrast, the cytoskeletal and ion transport effects were replicated by hydrolyzing PtdIns(4,5)P 2 with a membrane-targeted 5-phosphatase or by occluding the inositide using high-avidity tandem PH domain constructs. (rupress.org)
  • Among weaker daf-2 alleles there exist distinct mutant classes that differ in epistatic interactions with mutations in other genes. (genetics.org)
  • Two distinct domains within CIITA mediate self-association: involvement of the GTP-binding and leucine-rich repeat domains. (unc.edu)
  • The differential substrate preferences and activation modes of the distinct PI 3-kinase classes have important consequences for their functions. (biologists.org)
  • Furthermore, our results demonstrated a remarkably high degree of congruence in exosomal small non-coding RNA content between two distinct leishmania species, which argues for a conserved mechanism for exosomal RNA packaging in leishmania.My second objective was to investigate whether macrophage miRNA expression is modulated during leishmania infection. (ubc.ca)
  • Cellular 3-phosphoinositides are generated through the actions of a family of PI 3-kinases and appear to have regulatory roles in multiple cell functions. (sciencemag.org)
  • The class II phosphatidylinositol 3 kinase C2beta is required for the activation of the K+ channel KCa3.1 and CD4 T-cells. (ox.ac.uk)
  • We previously showed that nucleoside diphosphate kinase beta (NDPK-B), a mammalian histidine kinase, directly phosphorylates and activates KCa3.1 and is required for the activation of human CD4 T lymphocytes. (ox.ac.uk)
  • Cutting edge: activation of HIV-1 transcription by the MHC class II transactivator. (unc.edu)
  • Direct activation of human dendritic cells by particle-bound but not soluble MHC class II ligand. (invivogen.com)
  • Pubmed ID: 18802089 Short-lived TCR microclusters and a longer-lived protein kinase Ctheta-focusing central supramolecular activation cluster (cSMAC) have been defined in model immunological synapses (IS). (jove.com)
  • As IQGAP1 has been shown to interact with mTOR and with the mTORC1 activators ERK1/2, we propose that IQGAP1 serves as a scaffold for OspB activation of mTORC1. (prolekare.cz)
  • The dynamics of PI(3)K products PI(3,4,5)P(3)-PI(3,4)P(2) during neutrophil migration were visualized in living zebrafish, revealing that PI(3)K activation at the leading edge is critical for neutrophil motility in intact tissues. (nih.gov)
  • A series of sequentially activated protein kinases stimulated in response to 3-phosphoinositides causes activation of the p70 ribosomal protein S6 kinase ( 15 ). (sciencemag.org)
  • Several protein targets of 3-phosphoinositides have been identified. (sciencemag.org)
  • The encoded protein contains two SH2 domains through which it binds activated protein tyrosine kinases to regulate their activity. (nih.gov)
  • Tyrosine kinase c-Abl couples RNA polymerase II transcription to DNA double-strand breaks. (abcam.com)
  • Phosphatidylinositol 3-kinases are a family of dual specificity lipid/protein kinases. (embl.de)
  • Bioorg Med Chem Lett ;28(2):113-116, 2018 01 15. (bireme.br)
  • Deffrennes V, Vedrenne J, Stolzenberg MC, Piskurich J, Barbieri G, Ting JP, Charron D, Alcaide-Loridan C. Constitutive expression of MHC class II genes in melanoma cell lines results from the transcription of class II transactivator abnormally initiated from its B cell-specific promoter . (unc.edu)
  • In an attempt to identify novel susceptibility genes predisposing to early-onset diabetes (EOD), we performed a genome-wide scan using 433 markers in 222 individuals (119 with diabetes) from 29 Scandinavian families with ≥2 members with onset of diabetes ≤45 years. (diabetesjournals.org)
  • During the past few years, several monogenic forms of early-onset diabetes (EOD) have been described, including genes that cause maturity-onset diabetes of the young (MODY) and maternally inherited diabetes and deafness (MIDD) ( 3 , 4 ). (diabetesjournals.org)
  • 50 different mutations have been identified in both the HNF-1 α and the GCK genes ( 3 , 5 ). (diabetesjournals.org)
  • Between 11 and 45% of families that fulfill MODY criteria do not have mutations in known MODY genes (MODYX) ( 3 , 8 , 17 - 20 ). (diabetesjournals.org)
  • Involvement of class II phosphoinositide 3-kinase α-isoform in antigen-induced degranulation in RBL-2H3 cells. (nih.gov)
  • PI3KC2β was furthermore found to co-immunoprecipitate together with PKCβ (protein kinase C β isoform). (uzh.ch)
  • Not only are its metabolites critical for signal transduction, but PtdIns(4,5)P 2 itself serves multiple regulatory functions in the cell. (rupress.org)
  • CIITA is solely expressed on professional APCs however, non-professional APCs can also regulate CIITA activity and MHC II expression. (wikipedia.org)
  • 3. brain: parts the regulate bp. (brainscape.com)
  • The Tor kinases regulate responses to nutrients and control cell growth. (genetics.org)
  • We find that Tor1 does not regulate the known function of the class C Vps complex in protein sorting. (genetics.org)
  • In the ERK MAP kinase cascade, activated Raf-1, a serine-threonine kinase, initiates the signaling cascade through MEK, which in turn phosphorylates a second serine-threonine kinase ERK. (aacrjournals.org)
  • By contrast, the class III PI 3-kinases, represented by a single species (hVps34) in humans, have a relatively high activity even in resting cells. (biologists.org)
  • GRP1 binds phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P 3 ] through a pleckstrin homology (PH) domain and displays a region of high sequence similarity to the yeast Sec7 protein. (sciencemag.org)
  • Crystal structures of C2ALPHA-PI3 kinase PX-domain domain indicate conformational change associated with ligand binding. (guidetopharmacology.org)
  • The functional importance of the metabolites generated from PtdIns(4,5)P 2 has been convincingly established by pharmacological means. (rupress.org)