Class Ib Phosphatidylinositol 3-Kinase: 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.Phosphatidylinositol 3-Kinases: 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.Phosphatidylinositol Phosphates: Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.1-Phosphatidylinositol 4-Kinase: 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.Phosphatidylinositol 4,5-Diphosphate: 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)Phosphatidylinositols: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Phosphotransferases (Alcohol Group Acceptor): A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.Histocompatibility Antigens Class I: Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.MAP Kinase Signaling System: 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.ChromonesAndrostadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.MorpholinesProto-Oncogene Proteins c-akt: 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.Signal Transduction: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.Calcium-Calmodulin-Dependent 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)Ribonucleotide ReductasesMolecular Sequence Data: 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.src-Family Kinases: 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.Protein Kinase C: 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.HLA-G Antigens: Class I human histocompatibility (HLA) surface antigens encoded by alleles on locus B of the HLA complex. The HLA-G antigens are considered non-classical class I antigens due to their distinct tissue distribution which differs from HLA-A; HLA-B; and HLA-C antigens. Note that several isoforms of HLA-G antigens result from alternative splicing of messenger RNAs produced from the HLA-G*01 allele.Enzyme Activation: 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.Mexiletine: Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.Amino Acid Sequence: 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.Proto-Oncogene Proteins: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Mitogen-Activated Protein Kinase 1: 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.p38 Mitogen-Activated Protein Kinases: 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-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Protein Binding: 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.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Ribosomal Protein S6 Kinases: A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.Mitogen-Activated Protein Kinase 3: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.Kinetics: The rate dynamics in chemical or physical systems.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.JNK Mitogen-Activated Protein Kinases: A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Hominidae: Family of the suborder HAPLORHINI (Anthropoidea) comprising bipedal primate MAMMALS. It includes modern man (HOMO SAPIENS) and the great apes: gorillas (GORILLA GORILLA), chimpanzees (PAN PANISCUS and PAN TROGLODYTES), and orangutans (PONGO PYGMAEUS).Catarrhini: An infraorder of PRIMATES comprised of the families CERCOPITHECIDAE (old world monkeys); HYLOBATIDAE (siamangs and GIBBONS); and HOMINIDAE (great apes and HUMANS). With the exception of humans, they all live exclusively in Africa and Asia.Scandentia: An order of the class MAMMALS that consists of one family, TUPAIIDAE (tree shrews), 5 genera (one of which is TUPAIA), and 16 species. Their recent distribution is from India to the Philippines, southern China to Java, Borneo, Sumatra, Bali, and other islands in those regions.Proton-Translocating ATPases: Multisubunit enzymes that reversibly synthesize ADENOSINE TRIPHOSPHATE. They are coupled to the transport of protons across a membrane.

Role of the cAMP and MAPK pathways in the transformation of mouse 3T3 fibroblasts by a TSHR gene constitutively activated by point mutation. (1/144)

Constitutive activating mutations of the TSHR gene, have been detected in about 30 per cent of hyperfunctioning human thyroid adenomas and in a minority of differentiated thyroid carcinomas. The mutations activating the TSHR gene(s) in the thyroid carcinomas, were located at the codon 623 changing an Ala to a Ser (GCC-->TCC) or in codon 632 changing a Thr to Ala or Ile (ACC-->GCC or ACC-->ATC). In order to study if the constitutively activated TSHR gene(s) has played a role in the determination of the malignant phenotype presented by these tumors, we investigated: (1) the transforming capacity after transfection of mouse 3T3 cells, of a TSHR cDNA activated by an Ala-->Ser mutation in codon 623 or an Thr-->Ile mutation in codon 632 and (2) the pathway(s) eventually responsible(s) for the malignant phenotype of the cells transformed by these constitutively activated TSHR cDNAs. Our results show that (1) the TSHR(M623) or (M632) cDNAs give rise to 3T3 clones presenting a fully neoplastic phenotype (growth in agar and nude mouse tumorigenesis); this phenotype was weaker in the cells transformed by the 632 cDNA; (2) suggest that the fully transformed phenotype of our 3T3 cells, may be the consequence of the additive effect of the activation of at least two different pathways: the cAMP pathway through G(alpha)s and the Ras dependent MAPK pathway through G(beta)gamma and PI3K and (3) show that the PI3K isoform playing a key role as an effector in the MAPK pathway activation in our 3T3-transformed cells is PI3Kgamma. Signaling from PI3Kgamma to MAPK appears to require in our murine cellular system a tyrosine kinase (still not characterized), Shc, Grb2, Sos, Ras and Raf. It is proposed that the constitutively activated TSHR genes detected in the thyroid carcinomas, may have played an oncogenic role, participating in their development through these two pathways.  (+info)

Up-regulation of endothelial nitric-oxide synthase promoter by the phosphatidylinositol 3-kinase gamma /Janus kinase 2/MEK-1-dependent pathway. (2/144)

Our recent study indicates that lysophosphatidylcholine (LPC) enhances Sp1 binding and Sp1-dependent endothelial nitric oxide synthase (eNOS) promoter activity via the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 (MEK-1) signaling pathway (Cieslik, K., Lee, C.-M., Tang, J.-L., and Wu, K. K. (1999) J. Biol. Chem. 274, 34669-34675). To identify upstream signaling molecules, we transfected human endothelial cells with dominant negative and active mutants of Ras and evaluated their effects on eNOS promoter activity. Neither mutant altered the basal or LPC-induced eNOS promoter function. By contrast, a dominant negative mutant of phosphatidylinositol 3-kinase gamma (PI-3Kgamma) blocked the promoter activity induced by LPC. Wortmannin and LY 294002 had a similar effect. AG-490, a selective inhibitor of Janus kinase 2 (Jak2), also reduced the LPC-induced Sp1 binding and eNOS promoter activity to the basal level. LPC induced Jak2 phosphorylation, which was abolished by LY 294002 and the dominant negative mutant of PI-3Kgamma. LY 294002 and AG-490 abrogated MEK-1 phosphorylation induced by LPC but had no effect on Raf-1. These results indicate that PI-3Kgamma and Jak2 are essential for LPC-induced eNOS promoter activity. This signaling pathway was sensitive to pertussis toxin, suggesting the involvement of a G(i) protein in PI-3Kgamma activation. These results indicate that LPC enhances Sp1-dependent eNOS promoter activity by a pertussis toxin-sensitive, Ras-independent novel pathway, PI-3Kgamma/Jak2/MEK-1/ERK1/2.  (+info)

Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products. (3/144)

Morphologic polarity is necessary for the motility of mammalian cells. In leukocytes responding to a chemoattractant, this polarity is regulated by activities of small Rho guanosine triphosphatases (Rho GTPases) and the phosphoinositide 3-kinases (PI3Ks). Moreover, in neutrophils, lipid products of PI3Ks appear to regulate activation of Rho GTPases, are required for cell motility and accumulate asymmetrically to the plasma membrane at the leading edge of polarized cells. By spatially regulating Rho GTPases and organizing the leading edge of the cell, PI3Ks and their lipid products could play pivotal roles not only in establishing leukocyte polarity but also as compass molecules that tell the cell where to crawl.  (+info)

Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma. (4/144)

Ras activation of phosphoinositide 3-kinase (PI3K) is important for survival of transformed cells. We find that PI3Kgamma is strongly and directly activated by H-Ras G12V in vivo or by GTPgammaS-loaded H-Ras in vitro. We have determined a crystal structure of a PI3Kgamma/Ras.GMPPNP complex. A critical loop in the Ras binding domain positions Ras so that it uses its switch I and switch II regions to bind PI3Kgamma. Mutagenesis shows that interactions with both regions are essential for binding PI3Kgamma. Ras also forms a direct contact with the PI3Kgamma catalytic domain. These unique Ras/PI3Kgamma interactions are likely to be shared by PI3Kalpha. The complex with Ras shows a change in the PI3K conformation that may represent an allosteric component of Ras activation.  (+info)

A specific role of phosphatidylinositol 3-kinase gamma. A regulation of autonomic Ca(2)+ oscillations in cardiac cells. (5/144)

Purinergic stimulation of cardiomyocytes turns on a Src family tyrosine kinase-dependent pathway that stimulates PLCgamma and generates IP(3), a breakdown product of phosphatidylinositol 4,5-bisphosphate (PIP2). This signaling pathway closely regulates cardiac cell autonomic activity (i.e., spontaneous cell Ca(2+) spiking). PIP2 is phosphorylated on 3' by phosphoinositide 3-kinases (PI3Ks) that belong to a broad family of kinase isoforms. The product of PI3K, phosphatidylinositol 3,4,5-trisphosphate, regulates activity of PLCgamma. PI3Ks have emerged as crucial regulators of many cell functions including cell division, cell migration, cell secretion, and, via PLCgamma, Ca(2+) homeostasis. However, although PI3Kalpha and -beta have been shown to mediate specific cell functions in nonhematopoietic cells, such a role has not been found yet for PI3Kgamma. We report that neonatal rat cardiac cells in culture express PI3Kalpha, -beta, and -gamma. The purinergic agonist predominantly activates PI3Kgamma. Both wortmannin and LY294002 prevent tyrosine phosphorylation, and membrane translocation of PLCgamma as well as IP(3) generation in ATP-stimulated cells. Furthermore, an anti-PI3Kgamma, but not an anti-PI3Kbeta, injected in the cells prevents the effect of ATP on cell Ca(2+) spiking. A dominant negative mutant of PI3Kgamma transfected in the cells also exerts the same action. The effect of ATP was observed on spontaneous Ca(2+) spiking of wild-type but not of PI3Kgamma(2/2) embryonic stem cell-derived cardiomyocytes. ATP activates the Btk tyrosine kinase, Tec, and induces its association with PLCgamma. A dominant negative mutant of Tec blocks the purinergic effect on cell Ca(2+) spiking. Tec is translocated to the T-tubes upon ATP stimulation of cardiac cells. Both an anti-PI3Kgamma antibody and a dominant negative mutant of PI3Kgamma injected or transfected into cells prevent the latter event. We conclude that PI3Kgamma activation is a crucial step in the purinergic regulation of cardiac cell spontaneous Ca(2+) spiking. Our data further suggest that Tec works in concert with a Src family kinase and PI3Kgamma to fully activate PLCgamma in ATP-stimulated cardiac cells. This cluster of kinases provides the cardiomyocyte with a tight regulation of IP(3) generation and thus cardiac autonomic activity.  (+info)

Expression, purification, characterization and homology modeling of active Akt/PKB, a key enzyme involved in cell survival signaling. (6/144)

Akt is a serine/threonine kinase that plays a critical role in cell survival signaling and its activation has been linked to tumorigenesis. Up-regulation of Akt as well as its upstream regulator phosphatidylinositol-3 kinase (PI3K) has been found in many tumors and the negative regulator of this pathway PTEN/MMAC is a tumor suppressor. As a target for drug discovery, we have expressed and purified an active Akt1 enzyme from a recombinant baculovirus-infected Sf9 cell culture. Coexpression of Akt1 with the catalytic subunit of PI3K or treatment with okadaic acid during expression was found to generate an active enzyme in the insect cell culture system. We have optimized the kinase activity and developed a simple quantitative kinase assay using biotinylated peptide substrates. Using the purified active enzyme, we have characterized its physical, catalytic and kinetic properties. Since Akt is closely related to protein kinase C (PKC) and protein kinase A, the issue of obtaining selective inhibitors of this enzyme was addressed by comparison of the structures of catalytic domains of Akt and PKC, derived by homology modeling methods. A number of amino acid differences in the ATP binding regions of these kinases were identified, suggesting that selective inhibitors of Akt can be discovered. However, the ATP binding regions are highly conserved in the three isoforms of Akt implying that the discovery of isoform-selective inhibitors would be very challenging.  (+info)

Phosphoinositide 3-kinase gamma mediates angiotensin II-induced stimulation of L-type calcium channels in vascular myocytes. (7/144)

Previous results have shown that in rat portal vein myocytes the betagamma dimer of the G(13) protein transduces the angiotensin II-induced stimulation of calcium channels and increase in intracellular Ca(2+) concentration through activation of phosphoinositide 3-kinase (PI3K). In the present work we determined which class I PI3K isoforms were involved in this regulation. Western blot analysis indicated that rat portal vein myocytes expressed only PI3Kalpha and PI3Kgamma and no other class I PI3K isoforms. In the intracellular presence of an anti-p110gamma antibody infused by the patch clamp pipette, both angiotensin II- and Gbetagamma-mediated stimulation of Ca(2+) channel current were inhibited, whereas intracellular application of an anti-p110alpha antibody had no effect. The anti-PI3Kgamma antibody also inhibited the angiotensin II- and Gbetagamma-induced production of phosphatidylinositol 3,4,5-trisphosphate. In Indo-1 loaded cells, the angiotensin II-induced increase in [Ca(2+)](i) was inhibited by intracellular application of the anti-PI3Kgamma antibody, whereas the anti-PI3Kalpha antibody had no effect. The specificity of the anti-PI3Kgamma antibody used in functional experiments was ascertained by showing that this antibody did not recognize recombinant PI3Kalpha in Western blot experiments. Moreover, anti-PI3Kgamma antibody inhibited the stimulatory effect of intracellularly infused recombinant PI3Kgamma on Ca(2+) channel current without altering the effect of recombinant PI3Kalpha. Our results show that, although both PI3Kgamma and PI3Kalpha are expressed in vascular myocytes, the angiotensin II-induced stimulation of vascular L-type calcium channel and increase of [Ca(2+)](i) involves only the PI3Kgamma isoform.  (+info)

Resistance to thromboembolism in PI3Kgamma-deficient mice. (8/144)

Platelet aggregation and subsequent thrombosis are the major cause of ischemic diseases such as heart attack and stroke. ADP, acting via G protein-coupled receptors (GPCRs), is an important signal in thrombus formation and involves activation of phosphoinositide 3-kinases (PI3K). When platelets from mice lacking the G protein-activated PI3Kgamma isoform were stimulated with ADP, aggregation was impaired. Collagen or thrombin, however, evoked a normal response. ADP stimulation of PI3Kgamma-deficient platelets resulted in decreased PKB/Akt phosphorylation and alpha(IIb)beta(3) fibrinogen receptor activation. These effects did not influence bleeding time but protected PI3Kgamma-null mice from death caused by ADP-induced platelet-dependent thromboembolic vascular occlusion. This result demonstrates an unsuspected, well-defined role for PI3Kgamma downstream of ADP and suggests that pharmacological targeting of PI3Kgamma has a potential use as antithrombotic therapy.  (+info)

*Phosphoinositide 3-kinase

The regulatory p101 and catalytic p110γ subunits comprise the class IB PI3Ks and are encoded by a single gene each. The p85 ... "Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate". Nature. 332 (6165): ... 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 ...

*P110δ

"Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine ... Tyrosine kinases often operate near the plasma membrane and hence control the recruitment of p110δ to the plasma membrane where ... Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform also known as phosphoinositide 3-kinase (PI3K) ... The class I PI3Ks display a broad phosphoinositide lipid substrate specificity and include p110α, p110β and p110γ. p110α and ...

*Insulin-like growth factor 1 receptor

It belongs to the large class of tyrosine kinase receptors. This receptor mediates the effects of IGF-1, which is a polypeptide ... Cunningham ML, Horst JA, Rieder MJ, Hing AV, Stanaway IB, Park SS, Samudrala R, Speltz ML (2011). "IGF1R variants associated ... "Interaction of wild type and dominant-negative p55PIK regulatory subunit of phosphatidylinositol 3-kinase with insulin-like ... Tyrosine kinase receptors, including the IGF-1 receptor, mediate their activity by causing the addition of a phosphate groups ...

*Interleukin 15

Fyn and Lyn kinase. It also activates phosphatidylinositol 3-kinase (PI3K) and AKT signaling pathway and induce expression of ... Liew FY, McInnes IB (2002). "Role of interleukin 15 and interleukin 18 in inflammatory response". Ann. Rheum. Dis. 61 Suppl 2 ( ... Ahmad A, Ahmad R, Iannello A, Toma E, Morisset R, Sindhu ST (2005). "IL-15 and HIV infection: lessons for immunotherapy and ... kinase pathway and the phosphorylation of Lck (lymphocyte-activated protein tyrosine kinase) and Syk (spleen tyrosine kinase) ...
Results PDGF-directed invasion was completely inhibited by the pan PI3K inhibitor (1 uM). To define the role of the individual isoforms, we tested the effect of the isoform selective PI3K inhibitors. PI3Kdelta inhibition (INK007) significantly decreased the number of invading cells, with 60 ± 5% inhibition at 1 uM (p , 0.04). Similar results were observed with two other inhibitors with distinct chemical structures (CAL-101 and INK055). The PI3Kalpha inhibitor decreased invasion by 40 ± 5% while PI3Kbeta and PI3Kgamma inhibitors had no effect. Phalloidin staining was then used to visualise FLS actin rearrangement in response to PDGF with or without PI3K inhibitors. PI3Kdelta inhibition by INK007, CAL-101 and IPI-145 decreased lamellipodia formation by 50 ± 6% (p , 0.05). Similar inhibition was seen with the pan PI3K inhibitor, while the selective inhibitors of PI3Kalpha, PI3Kbeta or PI3Kgamma had no effect. We then hypothesised that PI3Kdelta might modulate activation of Rho GTPases in ...
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Type IB phosphoinositide 3OH-kinase (PI3K) is activated by G-protein βγ subunits (Gβγs). The enzyme is soluble and largely cytosolic in vivo. Its substrate, PtdIns(4,5)P2, and the Gβγs are localized at the plasma membrane. We have addressed the mechanism by which Gβγs regulate the PI3K using an in vitro approach. We used sedimentation assays and surface plasmon resonance to determine association of type IB PI3K with lipid monolayers and vesicles of varying compositions, some of which had Gβγs incorporated. Association and dissociation rate constants were determined. Our results indicated that in an assay situation in vitro the majority of PI3K will be associated with lipid vesicles, irrespective of the presence or absence of Gβγs. In line with this, a constitutively active membrane-targeted PI3K construct could still be activated substantially by Gβγs in vitro. We conclude that Gβγs activate type IB PI3K by a mechanism other than translocation to the plasma membrane.. ...
Sigma-Aldrich offers abstracts and full-text articles by [Michael Hannigan, Lijun Zhan, Zhong Li, Youxi Ai, Dianqing Wu, Chi-Kuang Huang].
The phosphatidylinositol 3 -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, translation, proliferation, growth, and survival. The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) stimulates class Ia and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5-triphosphate (PIP3) at the cell membrane. PIP3 in turn serves as a second messenger that helps to activate Akt. Once active, Akt can control key cellular processes by phosphorylating substrates involved in apoptosis, protein synthesis, metabolism, and cell cycle ...
The phosphatidylinositol 3 -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, translation, proliferation, growth, and survival. The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) stimulates class Ia and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5-triphosphate (PIP3) at the cell membrane. PIP3 in turn serves as a second messenger that helps to activate Akt. Once active, Akt can control key cellular processes by phosphorylating substrates involved in apoptosis, protein synthesis, metabolism, and cell cycle ...
The phosphatidylinositol 3 -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, translation, proliferation, growth, and survival. The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) stimulates class Ia and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5-triphosphate (PIP3) at the cell membrane. PIP3 in turn serves as a second messenger that helps to activate Akt. Once active, Akt can control key cellular processes by phosphorylating substrates involved in apoptosis, protein synthesis, metabolism, and cell cycle ...
PPP1CC overexpression lysate, 0.1 mg. Transient overexpression lysate of protein phosphatase 1, catalytic subunit, gamma isoform (PPP1CC)
pep:known chromosome:VEGA66:5:122158356:122175273:1 gene:OTTMUSG00000016349 transcript:OTTMUST00000039309 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Ppp1cc description:protein phosphatase 1, catalytic subunit, gamma isoform ...
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.
P48736: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform; PI3-kinase subunit gamma; PI3K-gamma; PI3Kgamma; PtdIns-3-kinase subunit gamma; 2.7.1.153; Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma; PtdIns-3-kinase subunit p110-gamma; p110gamma; Phosphoinositide-3-kinase catalytic gamma polypeptide; Serine/threonine protein kinase PIK3CG; 2.7.11.1; p120- ...
Caffeine is a naturally occurring methylxanthine that acts as a non-selective adenosine receptor antagonist. Epidemiological studies demonstrated habitual coffee drinking to be significantly associated with liver cancer survival. We aimed to investigate the effects of caffeine and its analog CGS 15943 on hepatocellular carcinoma (HCC) and pancreatic cancer adenocarcinoma (PDAC). We demonstrate that caffeine and CGS 15943 block proliferation in HCC and PDAC cell lines by inhibiting the PI3K/Akt pathway. Importantly a kinase profiling assay reveals that CGS 15943 targets specifically the catalytic subunit of the class IB PI3K isoform (p110ƴ). These data give mechanistic insight into the action of caffeine and its analogs and they identify these compounds as promising lead compounds to develop drugs that can specifically target this PI3K isoform whose key role in cancer progression is emerging.. ...
Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Dephosphorylates and activates transcription factor NFATC1. Dephosphorylates and inactivates transcription factor ELK1. Dephosphorylates DARPP32.
Ppp2r5c - Ppp2r5c (Myc-DDK-tagged) - Mouse protein phosphatase 2, regulatory subunit B (B56), gamma isoform (Ppp2r5c), transcript variant 3 available for purchase from OriGene - Your Gene Company.
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ID PK3CG_HUMAN Reviewed; 1102 AA. AC P48736; A4D0Q6; Q8IV23; Q9BZC8; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 04-APR-2006, sequence version 3. DT 22-NOV-2017, entry version 184. DE RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform; DE Short=PI3-kinase subunit gamma; DE Short=PI3K-gamma; DE Short=PI3Kgamma; DE Short=PtdIns-3-kinase subunit gamma; DE EC=2.7.1.153; DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma; DE Short=PtdIns-3-kinase subunit p110-gamma; DE Short=p110gamma; DE AltName: Full=Phosphoinositide-3-kinase catalytic gamma polypeptide; DE AltName: Full=Serine/threonine protein kinase PIK3CG; DE EC=2.7.11.1; DE AltName: Full=p120-PI3K; GN Name=PIK3CG; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE ...
Activation of phosphoinositide 3-kinase p110alpha isoform (PI3Kalpha) is cardioprotective in several cardiac pathologies. Marked impairment of left ventricular (LV) function characterizes the diabetic heart. The efficacy of PI3Kalpha cardioprotection has however not been sought in the diabetic heart. We tested the hypothesis that PI3Kalpha activation is protective against diabetes-induced LV dysfunction and remodeling in the mouse heart in vivo. Male cardiac-specific, constitutively-active PI3Kalpha transgenic (caPI3Kalpha; increases PI3Kalpha activity), dominant-negative PI3Kalpha transgenic (dnPI3Kalpha; decreases PI3Kalpha activity) and non-transgenic (Ntg) 6-wk old mice received streptozotocin (STZ, 55 mg/kg i.p./day for 5 days) or vehicle, and were followed for 12 weeks. Increases in blood glucose and glycated hemoglobin (GHB) with STZ were comparable among genotypes (see table). LV diastolic dysfunction was evident in Ntg diabetic mice, based on each of echocardiography-derived A wave ...
Ikbkg - Ikbkg (Myc-DDK-tagged ORF) - Rat inhibitor of kappaB kinase gamma (Ikbkg), (10 ug) available for purchase from OriGene - Your Gene Company.
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gammaisoform (EC 2.7.1.153) (PI3-kinase p110 subunit gamma) (PtdIns-3-kinase subunit p110) (PI3K) (PI3Kgamma) (p120-PI3K ...
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IC 87114 | PI3K p110δ inhibitor | IC87114 | CAS [371242-69-2] | Axon 2168 | Axon Ligand™ with >98% purity available from supplier Axon Medchem, prime source of life science reagents for your research
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Hypertensive cardiac hypertrophy (HCH) is a common cause of heart failure (HF), a major public health problem worldwide. However, the molecular bases of HCH have not been completely elucidated. Neuron-derived orphan receptor-1 (NOR-1) is a nuclear receptor whose role in cardiac remodelling is poorly understood. The aim of the present study was to generate a transgenic mouse over-expressing NOR-1 in the heart (TgNOR-1) and assess the impact of this gain-of-function on HCH. The CAG promoter-driven transgenesis led to viable animals that over-expressed NOR-1 in the heart, mainly in cardiomyocytes and also in cardiofibroblasts. Cardiomyocytes from TgNOR-1 exhibited an enhanced cell surface area and myosin heavy chain 7 (Myh7)/Myh6 expression ratio, and increased cell shortening elicited by electric field stimulation. TgNOR-1 cardiofibroblasts expressed higher levels of myofibroblast markers than wild-type (WT) cells (α 1 skeletal muscle actin (Acta1), transgelin (Sm22α)) and were more prone to ...
Familial incontinentia pigmenti (IP; MIM 308310) is a genodermatosis that segregates as an X-linked dominant disorder and is usually lethal prenatally in males. In affected females it causes highly variable abnormalities of the skin, hair, nails, teeth, eyes and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring. Cells expressing the mutated X chromosome are eliminated selectively around the time of birth, so females with IP exhibit extremely skewed X-inactivation. The reasons for cell death in females and in utero lethality in males are unknown. The locus for IP has been linked genetically to the factor VIII gene in Xq28 (ref. 3). The gene for NEMO (NF-kappaB essential modulator)/IKKgamma (IkappaB kinase-gamma) has been mapped to a position 200 kilobases proximal to the factor VIII locus. NEMO is required for the activation of the transcription ...
Harris RA, McQuilkin SJ, Paylor R, Abeliovich A, Tonegawa S, Wehner JM. Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors. Proc Natl Acad Sci USA 1995 Apr 25;92(9):3658-3662 ...
anafylaksi på grunn av dannelse anti-IgA-antistoffer ved IgA-mangel. RELIS har ikke funnet noen relevante treff ved søk på… aktuelle preparatet for å utelukke at preparatet kan inneholde IgA-komponenter, og at de er produsert i systemer hvor det ikke…. ...
Siz-le-ri bil-mem ama be-nim yaz ay-la-rında par-mak-la-rı-mı kı-pır-da-ta-cak ha-lim ol-maz sev-gi-li okur-la-rım. Şez-lon-gu-ma uzan-dı-ğım-da, kar-şım-da de-niz ol-ma-sa göz-le-ri-mi bi-le aç-mak is-te-mem. Göz-ka-pak-la-rı-nı kal-dı-ra-cak-sın da... Devamını okumak için başlığı tıklayınız.
Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3 (By similarity).
XIII. Pracovní setkání fyzikálních chemiků a elektrochemiků 13 th Workshop of Physical Chemists and Electrochemists sborník příspěvků Přírodovědecká fakulta Masarykovy univerzity Agronomická
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gtcaacaaa cctatctcg tccttgatg aacgttaaa ttagcgtag aagtaaaat gaaagttag tttaggaag gaagtgaga tgaaaccag tgttgtttg ttttcggta caaatttat tgttctcca tcgcacaat gtgcacgaa ttttgggcg tttttcccg cccctggat acagccagt tcattttag cggaagtct taatgaaag aaattgcca atcgaggac acgaagtta ctgtaatta gtccataca agccccaca atgcacctc ctaattata aaacgattg aaacgagtg acgtgatag aaaacagtg atgggttgg atttgtacg aacttgaca acgaatcgc tgtttaaaa atattttga cgacttacg aattcggga atattataa ctgagttta cattaaaaa ataaggaag tacaaaagt tgttacact cggatgtga gttttgatt tggtgattg tggagcaat ttttcaacg atgcaatga aaggcttcg cgaggcatt ttaacgcac ctttggtct tattcagtt cgatgggtt tgaccgaat ggaacaagg agtacatgg gaattccgg ccctgccat caattaatg cgatttctt acaccagtt acaccaacc gaatgaatt ttttcgaaa gaattcgca atttgatcg gcactattt tcgactatt gttaccgca agtgggtgt tttacccaa ttcagagag aatacttga gtagatatt tcccaaact ccatagatt ttgacgaaa taataaaca atgcaagcc taatgttac taaactcac attttacga cctccgaaa atgtccttt tgcccttca acatgatcg aaattgggg gcttccacg tcagtcaaa acccactaa gtaaggata tacaaaaaa ttttggacg ...
atgcatcac tgtgaaaac tgtaataaa caatttaca acccgtcaa tcacgacta cgccacgaa aagctctat tgtcaagtg gtcaaaaaa caggaaaat ggaggaccg gccgccaaa aaacagaaa atatgtcat tcaactgct agcaacaat tatatgtgc gttacatgt aatcaagaa attgctcca aagcttatt acggcccat gagagaagt agacagcat agaaataat tgtcaaagt actcccttg gaggatggg gtgtttgca ctcagcagt gcatttaaa tcacgcatc gcttcatat aggatttgt gatgagggc cattatatc gatttaaat gaatttatg gataaaatt cacaataaa ttacttaga cttattgtt tcacaaatt gaaaaattt agtacaatc aaaataaat ttggaatta tttggattg tataccatt gagtcaaaa aatatattt gatgtaaaa tctttcaat actactaac agaattgtc actttaggc acgaatatt aggaatatg ttgcatgac tttcaagaa gttattagt caaaaaatg atggatttt ttggaacga gattcaggc tggacactt gtgaaaatc ttacattta gaattaaat gtaaactat tacaatcca ttgaaagct tcatcgtat atcccacta ccgccaagc gtgaaaatg aagagggca atagttaat gttcaaaat caggatatt cattgtttt ggttggagt gtcgtagca gcagtgtgt ctacctatg ggaccagaa catttgccc agttcatat ccacattgg tcgacactt tttaatttc caaggtatt gaatttcct gtaaaactg gatagtatt gcaaaattt gaaagtcaa aataatgtc tctattaat gtttacgga ...
ABSTRACT. The AS/AGU rat has a recessive single point mutation in the gene coding for the gamma isoform of protein kinase C (PKC-γ) resulting in a failure to release dopamine in the striatum and impaired movement including a staggering gait, difficulty in initiating movement and a slight whole body tremor. This study examined the levels tyrosine hydroxylase, ubiquitin and parkin in individual SNC cell bodies. There was no evidence of a reduction in tyrosine hydroxylase levels although levels of ubiquitin and parkin were elevated in the cytoplasm. The findings support the hypothesis that the initial bar to dopamine availability in the striatum is reduced release, with substantia nigra cell death being a later phenomenon. 1. INTRODUCTION. The AS/AGU rat originated as a recessive mutation (agu) in a closed colony of Albino Swiss (AS) rats. The mutation is in the gene coding for the gamma isoform of protein kinase C [1]. The rats are characterized by a movement impairments including rigidity of the ...
Mice with homologous disruption of the interferon gamma (IFN-gamma) gene on the C57BL/6 background were infected with Leishmania major and the immune response assessed. In contrast to wild-type or heterozygous knockout mice, deficient animals were unable to restrict growth of the parasite and suffered lethal infection over 6-8 wk. Although wild-type and heterozygous littermates developed CD4+ cells that contained transcripts for IFN-gamma and lymphotoxin, typical of T helper type 1 (Th1) cells, the knockout mice developed CD4+ cells that contained transcripts for interleukin 4 (IL-4), IL-5, and IL-13, typical of Th2 cells. ELISPOT assays confirmed the reciprocal patterns of IFN-gamma or IL-4 production by T cells in similar frequencies in the respective groups of mice, and antibody analysis confirmed the presence of Th2-mediated isotype switching in the knockout mice. These data suggest that CD4+ T cells that normally respond to antigens by differentiation to Th1 cells default to the Th2 pathway ...
PI-3 kinase subunit gamma antibody for detecting human phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform. Validated on up to 12 cell lysates for western blotting. Try a trial size today.
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Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I α | JEMRegulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I α | JEM

Part of this work was supported by research grants from the Ministry of Education, Science, Sports and Culture; the Japan ... left) Fractions were separated by SDS-PAGE, transferred to PVDF membranes, and immunoblotted (IB) with anti-FcεRI γ-chain ... Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family. J. Biol. Chem. 271: ... The stress kinase mitogen-activated protein kinase kinase (MKK)7 is a negative regulator of antigen receptor and growth factor ...
more infohttp://jem.rupress.org/content/201/6/859

Pik3r6 - Phosphoinositide 3-kinase regulatory subunit 6 - Mus musculus (Mouse) - Pik3r6 gene & proteinPik3r6 - Phosphoinositide 3-kinase regulatory subunit 6 - Mus musculus (Mouse) - Pik3r6 gene & protein

"Ras is an indispensable coregulator of the class IB phosphoinositide 3-kinase p87/p110gamma.". Kurig B., Shymanets A., ... phosphatidylinositol 3-kinase signaling Source: GO_Central ,p>Inferred from Biological aspect of Ancestor,/p> ,p>A type of ... "Ras is an indispensable coregulator of the class IB phosphoinositide 3-kinase p87/p110gamma.". Kurig B., Shymanets A., ... "Ras is an indispensable coregulator of the class IB phosphoinositide 3-kinase p87/p110gamma.". Kurig B., Shymanets A., ...
more infohttps://www.uniprot.org/uniprot/Q3U6Q4

Pik3r5 - Phosphoinositide 3-kinase regulatory subunit 5 - Mus musculus (Mouse) - Pik3r5 gene & proteinPik3r5 - Phosphoinositide 3-kinase regulatory subunit 5 - Mus musculus (Mouse) - Pik3r5 gene & protein

... class IB Source: UniProtKB. Complete GO annotation on QuickGO ... ... PI3-kinase p101 subunit. Phosphatidylinositol 4,5-bisphosphate ... positive regulation of protein kinase B signaling Source: UniProtKB. *regulation of phosphatidylinositol 3-kinase activity ... State Secretariat for Education, Research and InnovationSERI. Wed like to inform you that we have updated our Privacy Notice ... p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and ...
more infohttps://www.uniprot.org/uniprot/Q5SW28

PIK3CG phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [Homo sapiens (human)] - Gene - NCBIPIK3CG phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [Homo sapiens (human)] - Gene - NCBI

PI3Kc_IB_gamma; Catalytic domain of Class IB Phosphoinositide 3-kinase gamma. ... C2_PI3K_class_I_gamma; C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks). smart00144. Location:203 → ... C2_PI3K_class_I_gamma; C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks). smart00144. Location:203 → ... C2_PI3K_class_I_gamma; C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks). smart00144. Location:203 → ...
more infohttps://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=Graphics&list_uids=5294

UniProt: P48736UniProt: P48736

... class IB; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase ... DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000403; PI3/4_kinase_cat_dom. DR InterPro; IPR036940; PI3/4_kinase_ ... KINASE_1; 1. DR PROSITE; PS00916; PI3_4_KINASE_2; 1. DR PROSITE; PS50290; PI3_4_KINASE_3; 1. DR PROSITE; PS51544; PI3K_ABD; 1. ... DR GO; GO:0016301; F:kinase activity; IDA:MGI. DR GO; GO:0035004; F:phosphatidylinositol 3-kinase activity; TAS:UniProtKB. DR ...
more infohttp://www.genome.jp/dbget-bin/www_bget?uniprot:P48736

Intracellular cAMP levels are higher in LDLR-/−p110γ | Open-iIntracellular cAMP levels are higher in LDLR-/−p110γ | Open-i

Class Ib Phosphatidylinositol 3-Kinase/genetics/physiology*. *Macrophages/cytology*. Minor. *Animals. *Cyclic AMP/metabolism ... We studied the role of phosphoinositol-3-kinase (PI3K) p110γ in the regulation of in situ apoptosis, macrophage proliferation ... We studied the role of phosphoinositol-3-kinase (PI3K) p110γ in the regulation of in situ apoptosis, macrophage proliferation ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC3750002_pone.0072674.g004&req=4

Frontiers | The Role of Class IA Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunits in Glioblastoma | OncologyFrontiers | The Role of Class IA Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunits in Glioblastoma | Oncology

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 IB PI3K is composed of one catalytic subunit p110γ encoded by PIK3CG (PI3K catalytic subunit γ) and two regulatory ...
more infohttps://www.frontiersin.org/articles/10.3389/fonc.2017.00312/full?utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Oncology&id=325085

Frontiers | The Role of Class IA Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunits in Glioblastoma | OncologyFrontiers | The Role of Class IA Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunits in Glioblastoma | Oncology

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 IB PI3K is composed of one catalytic subunit p110γ encoded by PIK3CG (PI3K catalytic subunit γ) and two regulatory ...
more infohttps://www.frontiersin.org/articles/10.3389/fonc.2017.00312/full

Immune response  - CCR3 signaling in eosinophils Pathway Map - PrimePCR | Life Science | Bio-RadImmune response - CCR3 signaling in eosinophils Pathway Map - PrimePCR | Life Science | Bio-Rad

PI3K class IB)/ PDK(PDPK1)/ PKC-zeta/ H-Ras/ c-Raf-1/ MEK1/2 kinases (MAPK/ERK) pathway [5], [6]. Although the upstream ... Regulation of eosinophil function by phosphatidylinositol-specific PLC and cytosolic PLA(2). American journal of physiology. ... Alternative RhoA pathways, via ROCK / LIM kinase 2 (LIMK2)/ Cofilin or DIA1/ Profilin, lead to rearrangement of Actin ... Classical Ca(2+) signaling involves myosin light chain kinase (MLCK) activation by Ca(2+)/Calmodulin complex, leading to MRLC ...
more infohttp://www.bio-rad.com/en-us/prime-pcr-assays/pathway/immune-response-ccr3-signaling-eosinophils

Immune response  - CCR3 signaling in eosinophils Pathway Map - PrimePCR | Life Science | Bio-RadImmune response - CCR3 signaling in eosinophils Pathway Map - PrimePCR | Life Science | Bio-Rad

PI3K class IB)/ PDK(PDPK1)/ PKC-zeta/ H-Ras/ c-Raf-1/ MEK1/2 kinases (MAPK/ERK) pathway [5], [6]. Although the upstream ... Regulation of eosinophil function by phosphatidylinositol-specific PLC and cytosolic PLA(2). American journal of physiology. ... Alternative RhoA pathways, via ROCK / LIM kinase 2 (LIMK2)/ Cofilin or DIA1/ Profilin, lead to rearrangement of Actin ... Classical Ca(2+) signaling involves myosin light chain kinase (MLCK) activation by Ca(2+)/Calmodulin complex, leading to MRLC ...
more infohttp://www.bio-rad.com/en-us/prime-pcr-assays/pathway/gpcr/immune-response-ccr3-signaling-eosinophils

PI3 kinase is important for Ras, MEK and Erk activation of Epo-stimulated human erythroid progenitors | BMC Biology | Full TextPI3 kinase is important for Ras, MEK and Erk activation of Epo-stimulated human erythroid progenitors | BMC Biology | Full Text

Biochemical studies with human cord blood-derived PEPs now show that Ras and the class Ib enzyme of the phosphatidylinositol-3 ... minimal levels of Epo which lead to a basal activation of the MEK and Erk kinases moderately activate the class Ib PI3 kinase ... The class Ib PI3K, PI3Kγ, is not regulated by p85 or similar subunits and instead interacts with a distinct regulatory protein ... Strong activation of class Ia PI3 kinases by SCF, but PI3Kγ activation by Epo. Starved PEPs were mock-stimulated (m), ...
more infohttps://preview-bmcbiol.biomedcentral.com/articles/10.1186/1741-7007-2-7

PI3K and PKC contribute to membrane depolarization mediated by α2-adrenoceptors in the canine isolated mesenteric vein | BMC...PI3K and PKC contribute to membrane depolarization mediated by α2-adrenoceptors in the canine isolated mesenteric vein | BMC...

Activation of PI3Kγ and PKCζ in response to exogenous NE and clonidine in the absence and presence of receptor and kinase ... Exogenous NE and clonidine (1 μM each) activated both PI3Kγ and PKCζ, and the activation of these kinases was abolished by ... and protein kinase C (PKC) are involved in the electrical field stimulation (EFS)-induced slow membrane depolarization (SMD) in ... In the present study we hypothesized that phosphatidylinositol 3-kinase (PI3K) ...
more infohttps://bmcphysiol.biomedcentral.com/articles/10.1186/1472-6793-5-9

A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with...A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with...

... pan-phosphatidylinositol 3-kinase inhibitor) plus paclitaxel, with and without bevacizumab or trastuzumab, or in combination ... Sixty-nine patients were enrolled; all experienced at least one adverse event (AE). Grade ≥ 3 AEs, serious AEs, and AEs leading ... Patients in parts 1 and 2, which comprised 3 + 3 dose escalation and cohort expansion stages, received pictilisib (60-330 mg) ... This phase Ib study (NCT00960960) evaluated pictilisib (GDC-0941; ...
more infohttps://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-018-1015-x

May | 2015 | alk geneMay | 2015 | alk gene

IB, II, and III classes, consists of a cataly tic domain and a regulatory domain and participates cell responses including cell ... 5 triphosphate to promote the activation of protein kinase B, an important downstream kinase that regulates glycogen and ... It is well established that insulin activates PI3K by linking to the insulin receptor and generating phosphatidylinositol 3,4, ... Insulin increases Na trans port by trafficking selleck kinase inhibitor ENaC subunits to the apical membrane in kidney cells ...
more infohttps://alkgene.com/2015/05

KEGG PATHWAY: PI3K-Akt signaling pathway - Homo sapiens (human)KEGG PATHWAY: PI3K-Akt signaling pathway - Homo sapiens (human)

... stimulates class Ia and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5- ... The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) ... The phosphatidylinositol 3 -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults ...
more infohttp://www.genome.jp/kegg-bin/show_pathway?hsa04151

Variation in a locus linked to platelet aggregation phenotype predicts intraparenchymal hemorrhagic volume.  - PubMed - NCBIVariation in a locus linked to platelet aggregation phenotype predicts intraparenchymal hemorrhagic volume. - PubMed - NCBI

2012 Apr;34(3):232-7. doi: 10.1179/1743132811Y.0000000080. Epub 2012 Mar 1. Research Support, Non-U.S. Govt ... Class Ib Phosphatidylinositol 3-Kinase. *PIK3CG protein, human. LinkOut - more resources. Full Text Sources. *Taylor & Francis ... Neurol Res. 2012 Apr;34(3):232-7. doi: 10.1179/1743132811Y.0000000080. Epub 2012 Mar 1. ...
more infohttps://phgkb.cdc.gov/PHGKB/phgHome.action?action=forward&dbsource=huge&id=71960

2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio.  - PubMed -...2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio. - PubMed -...

Class Ib Phosphatidylinositol 3-Kinase. *PIK3CG protein, human. *Proteasome Endopeptidase Complex. *proteasome activator PA700 ... Lin BD1, Carnero-Montoro E2, Bell JT2, Boomsma DI1, de Geus EJ1,3, Jansen R4, Kluft C5, Mangino M2,6, Penninx B4, Spector TD2, ... Epub 2017 Aug 3.. 2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte and platelet-to-lymphocyte ... 3. EMGO+ Institute for Health & Care Research, VU Medical Center, Amsterdam, The Netherlands.. 4. Department of Psychiatry, VU ...
more infohttps://phgkb.cdc.gov/PHGKB/phgHome.action?action=forward&dbsource=huge&id=158238

Recombinant cow PI 3 Kinase p110 alpha + PI 3 kinase p85 alpha protein (ab91351)Recombinant cow PI 3 Kinase p110 alpha + PI 3 kinase p85 alpha protein (ab91351)

Buy our Recombinant cow PI 3 Kinase p110 alpha + PI 3 kinase p85 alpha protein. Ab91351 is an active full length protein ... and phosphatidylinositol-4,5-bisphosphate (PIP2) in vitro. The class I members can be further subdivided into class IA and IB ... Class IA exists in three isoforms (p110alpha, p110beta and p110delta whereas the only class IB member is termed p110gamma. ... Class IA PI3Ks are activated by adaptor proteins such as Ras or BCAP, or tyrosine-kinase-associated receptors including antigen ...
more infohttp://www.abcam.com/recombinant-cow-pi-3-kinase-p110-alpha-pi-3-kinase-p85-alpha-protein-ab91351.html

KEGG PATHWAY: PI3K-Akt signaling pathway - Homo sapiens (human)KEGG PATHWAY: PI3K-Akt signaling pathway - Homo sapiens (human)

... stimulates class Ia and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5- ... The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) ... The phosphatidylinositol 3 -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults ...
more infohttp://www.kegg.jp/kegg-bin/show_pathway?hsa04151+672

KEGG PATHWAY: PI3K-Akt signaling pathway - Homo sapiens (human)KEGG PATHWAY: PI3K-Akt signaling pathway - Homo sapiens (human)

... stimulates class Ia and Ib PI3K isoforms, respectively. PI3K catalyzes the production of phosphatidylinositol-3,4,5- ... The binding of growth factors to their receptor tyrosine kinase (RTK) or G protein-coupled receptors (GPCR) ... The phosphatidylinositol 3 -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults ...
more infohttp://www.kegg.jp/kegg-bin/show_pathway?hsa04151+3320

Search Articles | University of Toronto LibrariesSearch Articles | University of Toronto Libraries

Class Ib Phosphatidylinositol 3-Kinase - deficiency , Pyrimidinones - pharmacology , Chromones - pharmacology , Morpholines - ... Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors , Linear Models , Protein Kinase Inhibitors - blood , Proto ... Class Ib Phosphatidylinositol 3-Kinase - genetics , Furans - pharmacology , Neovascularization, Pathologic , ... Protein Kinase Inhibitors - blood , Protein Kinase Inhibitors - administration & dosage , MAP Kinase Signaling System - drug ...
more infohttps://query.library.utoronto.ca/index.php/search/q?kw=SubjectTerms:Pyrimidinones%20-%20blood

September | 2012 | mirna mimicsSeptember | 2012 | mirna mimics

... the position of the ring of phosphatidylinositol 4,5 -. Diphosphate Class IB PI3K regulatory P101 and P110 together ? catalytic ... long-term strogenmangel maintained a result of AI activation of ERK MAP kinase and mTOR kinase PI canals le that are sensitive ... Specific inhibitors of PI3K isoforms of Class IA and IB-class to the specificity of the r t dissect each isoform. IC50 ... Finally, the effects of the suppression of Class IB P110C AS 6,252,424 are shown, which shows a parallel blocking Akt ...
more infohttps://mirnamimic.com/2012/09

PI3Kalpha, catalytic domain (IPR037704) | InterPro | EMBL-EBIPI3Kalpha, catalytic domain (IPR037704) | InterPro | EMBL-EBI

They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 ... Protein kinase-like domain superfamily (IPR011009). *Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily (IPR036940) ... Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3, ... Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class ...
more infohttps://www.ebi.ac.uk/interpro/entry/IPR037704

Ras Inhibitors, Agonists and Modulators - BOC SciencesRas Inhibitors, Agonists and Modulators - BOC Sciences

Of class I PI3Ks, subclass IA (PI3KCA, PI3KCB, PI3KCD) binds to the p85 regulatory subunit while subclass IB (PI3KCD) binds to ... Raf kinases: After activation by Ras, B-Raf phosphorylates and activates the dual specificity kinases, MEK1/2. MEK1/2 then ... Phosphatidylinositol 3-kinases: There are three classes of PI3Ks. Although both Class I and II PI3Ks have Ras-binding domains, ... Ras signals to three main effectors: Raf kinases, PI3-kinases, and the RalGDS family of exchange factors. These signaling ...
more infohttps://www.bocsci.com/tag/ras-322.html

Evidence for functional redundancy of class IA PI3K isoforms in insulin signalling | Biochemical JournalEvidence for functional redundancy of class IA PI3K isoforms in insulin signalling | Biochemical Journal

protein kinase B/Akt. INTRODUCTION. PI3Ks (phosphatidylinositol 3-kinases) catalyse the phosphorylation of the D-3 position of ... class IA and class IB. There is only one class IB PI3K (p110γ) and this operates downstream of heterotrimeric GPCRs (G-protein- ... To produce class IB PI3K, Sf21 insect cells were infected with baculovirus expressing N-terminal His-tagged bovine p110γ. The ... Recent genetic knock-in and pharmacological approaches have suggested that, of class IA PI3Ks (phosphatidylinositol 3-kinases ...
more infohttp://www.biochemj.org/content/404/3/449?ijkey=297ef317992c1aa5b423860bd6654a3d1d957da9&keytype2=tf_ipsecsha
  • 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)
  • These data show that PI 3-kinase is regulated by a number of mechanisms, and that Ras contributes to the activation of this lipid kinase synergistically with tyrosine kinases. (embl.de)
  • Tyrosine kinases often operate near the plasma membrane and hence control the recruitment of p110δ to the plasma membrane where its substrate PtdIns(4,5)P2 is found. (wikipedia.org)
  • Bovine PI 3-Kinase alpha differs from the Human enzyme in only 2 positions, K532R and S535C. (abcam.com)
  • The present invention relates to compounds of Formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X1, X2, X3, X4, R2, and R3 are each as defined herein. (organic-reaction.com)
  • Finally, the effects of the suppression of Class IB P110C AS 6,252,424 are shown, which shows a parallel blocking Akt activation in dosedependent decrease of cell proliferation and expression of collagen and SMA Go Labeled use. (mirnamimic.com)
  • A point mutation in this region, K227E, blocks the GTP-dependent interaction of PI 3-kinase p110alpha with Ras in vitro and the ability of Ras to activate PI 3-kinase in intact cells. (embl.de)
  • Results emphasize the physiological importance of phosphatidylinositol 3-kinase-gamma (PI3Kgamma) in restraining inflammation and promoting appropriate adaptive immune responses in both humans and mice. (nih.gov)
  • RT "PI3Kgamma modulates the cardiac response to chronic pressure overload RT by distinct kinase-dependent and -independent effects. (genome.jp)
  • To obtain the Tipifarnib Transferase full length sequence, specific Inhibitors,Modulators,Libraries primers based on both, globe artichoke and cardoon, partial cDNA sequences, were designed for 3 and 5 end amplification as described in Comino et al. (alkgene.com)
  • This has occurred concurrently with technological advances allowing rational drug design and development (such as tyrosine kinase inhibitors, monoclonal antibodies and anti-sense oligonucleotides). (intechopen.com)
  • ERK1/2 substrates include a wide variety of transcription factors, kinases and phosphatases, cytoskeletal proteins, signaling proteins, and apoptotic proteins and proteinases. (bocsci.com)
  • 15 ]. DAG activates protein kinases C (e.g. (bio-rad.com)
  • InsP 3 has the capacity to release cytosolic Ca 2+ from intracellular stores, which then activates Ca 2+ -activated Cl - channels (ClC Ca ) and membrane depolarization, required for opening of voltage-operated calcium channels (VOCC) and Ca 2+ influx. (biomedcentral.com)
  • PI 3-kinase: structural and functional analysis of intersubunit interactions. (embl.de)