Class Ia Phosphatidylinositol 3-Kinase: A phosphatidylinositol 3-kinase subclass that includes enzymes formed through the heterodimerization of a p110 catalytic and a p85, p55, or p50 regulatory subunit. This subclass of enzymes is a downstream target of TYROSINE KINASE RECEPTORS and 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.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.MEDLINE: The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).Serial Publications: Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)Biological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Galectins: A class of animal lectins that bind specifically to beta-galactoside in a calcium-independent manner. Members of this class are distiguished from other lectins by the presence of a conserved carbohydrate recognition domain. The majority of proteins in this class bind to sugar molecules in a sulfhydryl-dependent manner and are often referred to as S-type lectins, however this property is not required for membership in this class.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.Phagosomes: Membrane-bound cytoplasmic vesicles formed by invagination of phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material.Allergy and Immunology: A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder.Lysosomes: 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)Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides.Endosomes: Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.Period Circadian Proteins: Circadian rhythm signaling proteins that influence circadian clock by interacting with other circadian regulatory proteins and transporting them into the CELL NUCLEUS.Cryptochromes: Flavoproteins that function as circadian rhythm signaling proteins in ANIMALS and as blue-light photoreceptors in PLANTS. They are structurally-related to DNA PHOTOLYASES and it is believed that both classes of proteins may have originated from an earlier protein that played a role in protecting primitive organisms from the cyclical exposure to UV LIGHT.GermanyFlavoproteinsPhotoreceptor Cells, Invertebrate: Specialized cells in the invertebrates that detect and transduce light. They are predominantly rhabdomeric with an array of photosensitive microvilli. Illumination depolarizes invertebrate photoreceptors by stimulating Na+ influx across the plasma membrane.Vacuolar Sorting Protein VPS15: A 150 kDa protein serine-threonine kinase that is found as a regulatory subunit of the class III phosphatidylinositol 3-kinases. The protein is believed to play an important role in the regulation of vesicular trafficking with the cell.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Syntaxin 1: A neuronal cell membrane protein that combines with SNAP-25 and SYNAPTOBREVIN 2 to form a SNARE complex that leads to EXOCYTOSIS.SNARE Proteins: A superfamily of small proteins which are involved in the MEMBRANE FUSION events, intracellular protein trafficking and secretory processes. They share a homologous SNARE motif. The SNARE proteins are divided into subfamilies: QA-SNARES; QB-SNARES; QC-SNARES; and R-SNARES. The formation of a SNARE complex (composed of one each of the four different types SNARE domains (Qa, Qb, Qc, and R)) mediates MEMBRANE FUSION. Following membrane fusion SNARE complexes are dissociated by the NSFs (N-ETHYLMALEIMIDE-SENSITIVE FACTORS), in conjunction with SOLUBLE NSF ATTACHMENT PROTEIN, i.e., SNAPs (no relation to SNAP 25.)Qb-SNARE Proteins: A subfamily of Q-SNARE PROTEINS which occupy the same position in the SNARE complex as the N-terminal SNARE domain of SNAP-25 and which also are most similar to the N-terminal region of SNAP-25 in their AMINO ACID SEQUENCE.R-SNARE Proteins: SNARE proteins where the central amino acid residue of the SNARE motif is an ARGININE. They are classified separately from the Q-SNARE PROTEINS where the central amino acid residue of the SNARE motif is a GLUTAMINE. This subfamily contains the vesicle associated membrane proteins (VAMPs) based on similarity to the prototype for the R-SNAREs, VAMP2 (synaptobrevin 2).Qa-SNARE Proteins: A subfamily of Q-SNARE PROTEINS which occupy the same position as syntaxin 1A in the SNARE complex and which also are most similar to syntaxin 1A in their AMINO ACID SEQUENCE. This subfamily is also known as the syntaxins, although a few so called syntaxins are Qc-SNARES.Vesicular Transport Proteins: A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.Cystatin B: An intracellular cystatin subtype that is found in a broad variety of cell types. It is a cytosolic enzyme inhibitor that protects the cell against the proteolytic action of lysosomal enzymes such as CATHEPSINS.Social Media: Platforms that provide the ability and tools to create and publish information accessed via the INTERNET. Generally these platforms have three characteristics with content user generated, high degree of interaction between creator and viewer, and easily integrated with other sites.National Library of Medicine (U.S.): An agency of the NATIONAL INSTITUTES OF HEALTH concerned with overall planning, promoting, and administering programs pertaining to advancement of medical and related sciences. Major activities of this institute include the collection, dissemination, and exchange of information important to the progress of medicine and health, research in medical informatics and support for medical library development.Publications: Copies of a work or document distributed to the public by sale, rental, lease, or lending. (From ALA Glossary of Library and Information Science, 1983, p181)Journal Impact Factor: A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.Newspapers: Publications printed and distributed daily, weekly, or at some other regular and usually short interval, containing news, articles of opinion (as editorials and letters), features, advertising, and announcements of current interest. (Webster's 3d ed)Bibliometrics: The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Rhodamine 123: A fluorescent probe with low toxicity which is a potent substrate for P-glycoprotein and the bacterial multidrug efflux transporter. It is used to assess mitochondrial bioenergetics in living cells and to measure the efflux activity of P-glycoprotein in both normal and malignant cells. (Leukemia 1997;11(7):1124-30)Leukemia P388: An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Molecular 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.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.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.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Class I Phosphatidylinositol 3-Kinases: A phosphatidylinositol 3-kinase subclass that includes enzymes with a specificity for 1-phosphatidylinositol, 1-phosphatidylinositol 4-phosphate, and 1-phosphatidylinositol 4,5-bisphosphate. Members of this enzyme subclass are activated by cell surface receptors and occur as heterodimers of enzymatic and regulatory subunits.Stem Cell Research: Experimentation on STEM CELLS and on the use of stem 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.

p110beta is up-regulated during differentiation of 3T3-L1 cells and contributes to the highly insulin-responsive glucose transport activity. (1/118)

Activation of p85/p110 type phosphatidylinositol kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis. The enzyme exists as a heterodimer containing a regulatory subunit (e.g. p85alpha) and one of two widely distributed isoforms of the p110 catalytic subunit: p110alpha or p110beta. In the present study, we compared the two isoforms in the regulation of insulin action. During differentiation of 3T3-L1 cells into adipocytes, p110beta was up-regulated approximately 10-fold, whereas expression of p110alpha was unaltered. The effects of the increased p110 expression were further assessed by expressing epitope tagged p110beta and p110alpha in 3T3-L1 cells using adenovirus transduction systems, respectively. In vitro, the basal lipid kinase activity of p110beta was lower than that of p110alpha. When p110alpha and p110beta were overexpressed in 3T3-L1 adipocytes, exposing cells to insulin induced each of the subunits to form complexes with p85alpha and tyrosine-phosphorylated IRS-1 with similar efficiency. However, whereas the kinase activity of p110beta, either endogenous or exogeneous, was markedly enhanced by insulin stimulation, only very small increases of the activity of p110alpha were observed. Interestingly, overexpression of p110beta increased insulin-induced glucose uptake by 3T3-L1 cells without significantly affecting basal glucose transport, whereas overexpression of p110alpha increased both basal and insulin-stimulated glucose uptake. Finally, microinjection of anti-p110beta neutralizing antibody into 3T3-L1 adipocytes abolished insulin-induced translocation of GLUT4 to the cell surface almost completely, whereas anti-p110alpha neutralizing antibody did only slightly. Together, these findings suggest that p110beta plays a crucial role in cellular activities evoked acutely by insulin.  (+info)

Characterization of a new family of protein kinases from Arabidopsis containing phosphoinositide 3/4-kinase and ubiquitin-like domains. (2/118)

At least two of the genes predicted to encode type II PI4K (phosphoinositide 4-kinase) in Arabidopsis thaliana (thale cress), namely AtPI4Kgamma4 and AtPI4Kgamma7, encode enzymes with catalytic properties similar to those of members of the PIKK (phosphoinositide kinase-related kinase) family. AtPI4Kgamma4 and AtPI4Kgamma7 undergo autophosphorylation and phosphorylate serine/threonine residues of protein substrates, but have no detectable lipid kinase activity. AtPI4Kgamma4 and AtPI4Kgamma7 are members of a subset of five putative AtPI4Ks that contain N-terminal UBL (ubiquitin-like) domains. In vitro analysis of AtPI4Kgamma4 indicates that it interacts directly with, and phosphorylates, two proteins involved in the ubiquitin-proteasome system, namely UFD1 (ubiquitin fusion degradation 1) and RPN10 (regulatory particle non-ATPase 10). On the basis of the present results, we propose that AtPI4Kgamma4 and AtPI4Kgamma7 should be designated UbDKgamma4 and UbDKgamma7 (ubiquitin-like domain kinases gamma4 and gamma7). These UBL-domain-containing AtPI4Ks correspond to a new PIKK subfamily of protein kinases. Furthermore, UFD1 and RPN10 phosphorylation represents an additional mechanism by which their function can be regulated.  (+info)

Lysophosphatidic acid inhibits the cytotoxic activity of NK cells: involvement of Gs protein-mediated signaling. (3/118)

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Phosphoinositide 3-kinase delta inhibitor suppresses interleukin-17 expression in a murine asthma model. (4/118)

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Platelet endothelial cell adhesion molecule-1 regulates collagen-stimulated platelet function by modulating the association of phosphatidylinositol 3-kinase with Grb-2-associated binding protein-1 and linker for activation of T cells. (5/118)

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Arsenite stabilizes HIF-1alpha protein through p85alpha-mediated up-regulation of inducible Hsp70 protein expression. (6/118)

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Activation of the phosphoinositide-3-kinase and mammalian target of rapamycin signaling pathways are associated with shortened survival in patients with malignant peritoneal mesothelioma. (7/118)

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Nature and duration of growth factor signaling through receptor tyrosine kinases regulates HSV-1 latency in neurons. (8/118)

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*Phosphoinositide 3-kinase

... they are further divided between IA and IB subsets on sequence similarity. Class IA PI3K is composed of a heterodimer between a ... "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) ... Like the other class IA PI3Ks, p110δ is a catalytic subunit, whose activity and subcellular localisation are controlled by an ...

*USP8

Row PE, Prior IA, McCullough J, et al. (2006). "The ubiquitin isopeptidase UBPY regulates endosomal ubiquitin dynamics and is ... Janssen JW, Schleithoff L, Bartram CR, Schulz AS (May 1998). "An oncogenic fusion product of the phosphatidylinositol 3-kinase ... D'Andrea A, Pellman D (1999). "Deubiquitinating enzymes: a new class of biological regulators". Crit. Rev. Biochem. Mol. Biol. ... Kato M, Miyazawa K, Kitamura N (2001). "A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding ...

*Platelet-derived growth factor receptor

The class IA phospholipid kinase, PI-3 kinase, is activated by the majority of RTKs. Similarly to other SH2 domain-containing ... Valius M, Kazlauskas A (April 1993). "Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of ... Dimerization is a prerequisite for the activation of the kinase. Kinase activation is visualized as tyrosine phosphorylation of ... which in many cases also are substrates for the kinase. The second part of the tyrosine kinase domain in the PDGFβ receptor is ...

*Nicotinic acid adenine dinucleotide phosphate

Graeff, R; Liu, Q; Kriksunov, IA; Hao, Q; Lee, HC (2006-09-29). "Acidic residues at the active sites of CD38 and ADP-ribosyl ... Their luminal pH is one characteristic that distinguishes a given vesicle class from another: where endosomes are weakly acidic ... Phosphatidylinositol 3,5-bisphosphate, PI(3,5)P2 and also by metabolic state (via ATP and mTOR). As a result of this, several ... P₂ and multiple protein kinases". EMBO J. 33 (5): 501-11. doi:10.1002/embj.201387035. PMC 3989630 . PMID 24502975. Grimm, C; ...
Pik3r1 encodes p85α, a regulatory subunit of class IA phosphatidylinositol 3-kinases (PI3Ks). To form a functional class I PI3K, a p110 catalytic subunit forms a heterodimer with a p85 regulatory subunit (3;4). There are three class IA p110 subunits (p110α, p110β, and p110δ [see the record for stinger]) encoded by Pik3ca, Pik3cb, and Pik3cd, respectively, and one class IB p110 subunit, p110γ (encoded by Pik3cg). Five class IA regulatory subunits are encoded by three distinct genes (Pik3r1 (p85α, p55α, p50α), Pik3r2 (p85β) and Pik3r3 (p55γ); p85α, p55α, and p50α are splice variants of Pik3r1 (Figure 10) (5-7). In activated cells, the p85 subunit recruits the p110 subunit to the plasma membrane and activates it (7-9). Conversely, the p85 subunit also inhibits the enzymatic activity of the p110 subunit in quiescent cells (10). The p85 subunits also mediate the interactions of the PI3Ks with the cytoplasmic domains of receptors as well as with adaptor proteins (11). p85α has several ...
26S Proteasome regulatory subunit p55, 50 µg. The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator.
26S Proteasome regulatory subunit p55, 50 µg. The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator.
Class IA phosphoinositide 3-kinases (PI3Ks) are heterodimers consisting of a catalytic subunit (p110α, p110β or p110δ) in complex with one of five regulatory subunits (collectively called the `p85s). The interaction of the Src homology 2 (SH2) domains of p85 with phosphotyrosine residues in receptors and adaptor molecules facilitates recruitment of the class IA PI3Ks to the membrane, where they generate lipid second messenger signals that control cell growth, proliferation, survival, intracellular traffic, cytoskeletal changes and cell migration (Vanhaesebroeck et al., 2001). Whereas p110α and p110β are ubiquitously expressed, p110δ expression is low in most cells (Sawyer et al., 2003) but highly enriched in leukocytes (Chantry et al., 1997; Vanhaesebroeck et al., 1997) and to a lesser extent in neurons (Eickholt et al., 2007). Some cancer cell lines, including some of breast and melanoma origin, can also express high levels of p110δ (Arcaro et al., 2002; Boller et al., 2008; Chaussade ...
The PI3K plays a major role in many aspects of cellular biology and is often hyperactivated in human cancers (1, 4). The PI3K family of enzymes has multifunctional roles regulating cellular growth, proliferation, differentiation, motility, intracellular trafficking, and metabolism (4). Three distinct classes of PI3K (class I, II, and III) have been characterized and grouped according to their structure and function. The class IA PI3Ks, which have been implicated in many human cancers, are activated downstream of receptor tyrosine kinases and G protein-coupled receptors (GPCRs) and via interaction with the activated RAS or RHO family of GTPases. Class IA PI3Ks are heterodimers, and each consists of a regulatory subunit p85 (p85α, p55α, or p50α isoforms encoded by PIK3R1, PIK3R2, or PIK3R3, respectively) and a catalytic subunit p110 (p110α, p110β, or p110δ isoforms encoded by PIK3CA, PIK3CB, or PIK3CD, respectively; refs. 1, 4). Class IB comprises a single catalytic subunit, p110δ, that ...
Elevated levels of systemic, liver-derived IGF-I and increased serum IGF-I:IGFBP-3 ratio have emerged as potential risk factors for cancers (19, 20, 21, 22) also known to frequently overexpress COX-2 (10 , 11 , 42, 43, 44) . Furthermore, as a recent study indicates, down-regulation of IGFBP-3 in stage I NSCLC predicts a shorter survival (45) . An IGF-autocrine growth loop also has been shown to operate in a number of tumor cell lines (26 , 46) . Therefore, we speculated that a functional link exists between tumor COX-2 and the IGF axis in NSCLC cells.. As hypothesized, COX-2 enhanced the IGF-related viability and proliferation of NSCLC cells (Figs. 1 ⇓ , 2 ⇓ , and 3 ⇓ ). The COX-2-enhanced viability and mitogenicity of IGFs in A549 cells were accompanied by the following: (1) facilitated autophosphorylation of IGF-IR (Fig. 3B) ⇓ ; (2) up-regulation of class IA PI3k signaling (Fig. 2) ⇓ ; and (3) down-regulation of IGFBP-3 expression (Fig. 6) ⇓ . All of these activities can be ...
Rabbit polyclonal 26S Proteasome regulatory subunit p55 antibody (ab156604) validated for WB and tested in Human. Immunogen corresponding to
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To modulate T cell function for cancer therapy one challenge is to selectively attenuate regulatory but not conventional CD4+ T cell subsets (Treg and Tconv). In this study we show how a functional dichotomy in Class IA PI3K isoforms in these two subsets of CD4+ T cells be exploited to target Treg while leaving Tconv intact. Studies employing isoform-specific PI3K inhibitors and a PI3Kδ-deficient mouse strain revealed that PI3Kα and PI3Kβ were functionally redundant with PI3Kδ in Tconv. Conversely, PI3Kδ was functionally critical in Treg, acting there to control TCR signaling, cell proliferation and survival. Notably, in a murine model of lung cancer, co-administration of a PI3Kδ-specific inhibitor with a tumor-specific vaccine decreased numbers of suppressive Treg and increased numbers of vaccine-induced CD8 T-cells within the tumor microenvironment, eliciting potent anti-tumor efficacy. Overall, our results offer a mechanistic rationale to employ PI3Kδ inhibitors to selectively target ...
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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 ...
Pex1p, Pex6p, and phosphoinositide- and GTP-bp associate with ECR membrane domains that can float to low density during centrifugation in a sucrose density grad
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In a series of studies spanning several years, Cantley and colleagues demonstrated that a kinase activity associated with the middle T oncoprotein is a phosphoinositide kinase,[7] that it is a novel type of phosphoinositide kinase that phosphorylates the 3 position on the inositol ring,[8] and that this phosphatidylinositol-3-kinase (PI-3-kinase) is activated by growth factors to produce novel 3-phosphorylated phosphoinositides, in particularly PtdIns(3,4,5)P3 [9] that had previously been identified in physiologically stimulated human neutrophils.[10] In subsequent years Cantley and colleagues identified critical aspects of the regulation of PI-3-kinase by growth factor receptors. Specifically, they discovered that the catalytic subunit p110 dimerizes with the regulatory subunit p85,[11] and that the SH2 domain of p85 specifically recognized phosphotyrosines[12] on growth factor receptors or adaptor proteins via the pY-X-X-M motif.[13][14]. The Cantley lab has also made seminal contributions ...
TY - JOUR. T1 - Assembly and molecular architecture of the phosphoinositide 3-kinase p85α homodimer. AU - LoPiccolo, Jaclyn. AU - Kim, Seung Joong. AU - Shi, Yi. AU - Wu, Bin. AU - Wu, Haiyan. AU - Chait, Brian T.. AU - Singer, Robert H.. AU - Sali, Andrej. AU - Brenowitz, Michael D.. AU - Bresnick, Anne R.. AU - Backer, Jonathan M.. PY - 2015/12/18. Y1 - 2015/12/18. N2 - Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that are activated by growth factor and G-protein-coupled receptors and propagate intracellular signals for growth, survival, proliferation, and metabolism. p85α, a modular protein consisting of five domains, binds and inhibits the enzymatic activity of class IA PI3K catalytic subunits. Here, we describe the structural states of the p85α dimer, based on data from in vivo and in vitro solution characterization. Our in vitro assembly and structural analyses have been enabled by the creation of cysteine-free p85α that is functionally equivalent to native p85α. ...
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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Current Black Lab researchers include doctoral, PharmD, graduate, and undergraduate students. Past lab members have achieved admission into a fellowship program at the American Association of Pharmaceutical Scientists and published a paper in Cancer Biology and Therapy related to inhibition of class IA PI3K enzymes in non-small cell lung cancer cells. More recently, a Black Lab member joined Experimental Biology 2015 to present multiple posters on cancer research ...
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... Path 7: Start: p 107 : skip footnote X : go to p. 111 p. 111 : skip footnote 129 : go to p 113 skip p 114 footnote 134 : skip p 114 footnote 135 stop p 114 footnote 136 : stop p 114 footnote K p 109 footnote K…
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Frequently present in pancreatic, colorectal and non-small cell lung carcinomas, oncogenic mutant K-Ras must be localised to the plasma membrane (PM) to be functional. Inhibitors of K-Ras PM localisation are therefore putative cancer chemotherapeutics. By screening a microbial extract library in a high conte
Reactivity: Rat (Rattus) - Sample Type: Cell Culture Supernatant, Plasma. | Order Phosphoinositide 3 Kinase, p85 alpha (PI3K p85a) ELISA Kit (ABIN772265).
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PIK3C2A - PIK3C2A (untagged)-Human phosphoinositide-3-kinase, class 2, alpha polypeptide (PIK3C2A) available for purchase from OriGene - Your Gene Company.
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  • Compelling evidence have emerged recently that indicate that the rapamycin-insensitive mammalian target of rapamycin inhibitor mTORC2 complex (mTOR in complex with rictor, Sin1, and mLst8) is PDK2 ( 3 - 7 ). (aacrjournals.org)
  • Further investigation of inhibitors of MRSA pyruvate kinase: Towards the conception of novel antimicrobial agents. (nih.gov)
  • Synthetic analogues of the marine bisindole deoxytopsentin: potent selective inhibitors of MRSA pyruvate kinase. (nih.gov)
  • Discovery and optimization of a new class of pyruvate kinase inhibitors as potential therapeutics for the treatment of methicillin-resistant Staphylococcus aureus infections. (nih.gov)
  • Unsupervised hierarchical cluster analysis shows select gene expression alterations in c.1380delA CDH1 SB.mhdgc-1 cells compared to a panel of sporadic gastric cancer cell lines with enrichment of ERK1-ERK2 (extracellular signal regulated kinase) and IP3 (inositol trisphosphate)/DAG (diacylglycerol) signaling as the top networks in c.1380delA SB.mhdgc-1 cells. (biomedcentral.com)
  • Their primary biochemical function is to phosphorylate the 3'-OH group in inositol lipids (Markman et al. (vjsonline.org)
  • Caspase-8 has also been implicated in the proinvasive effects of FASL in tumor cells ( 3 ). (aacrjournals.org)
  • The core class III PI(3)K complexes consist of Beclin 1, Vps34, and Vps15. (hep.com.cn)
  • Discovery of a 1,2-bis(3-indolyl)ethane that selectively inhibits the pyruvate kinase of methicillin-resistant Staphylococcus aureus over human isoforms. (nih.gov)
  • Class III seems to be primarily involved in the trafficking of proteins and vesicles. (wikipedia.org)
  • The conversion of PtdIns(4,5)P2 to PtdIns(3,4,5)P3 triggers signal transduction cascades controlled by PKB (also known as Akt), Tec family kinases and other proteins that contain PH domains. (wikipedia.org)
  • Subsequently, Cantley and colleagues demonstrated that in vivo the enzyme prefers PtdIns(4,5)P2 as a substrate, producing the novel phosphoinositide PtdIns(3,4,5)P3 previously identified in neutrophils The phosphoinositol-3-kinase family is divided into four different classes: Class I, Class II, Class III, and Class IV. (wikipedia.org)
  • 3. The method of claim 1, wherein the pancreatic β cell specific targeting moiety comprises an antibody or an aptamer. (freepatentsonline.com)
  • This results in rapid activation of H-Ras and subsequent activation of c-Raf-1 / MEK1(MAP2K1) and MEK2(MAP2K2) , ERK2 (MAPK1) cascade [ 2 ], [ 3 ]. (bio-rad.com)
  • Fig.1 A schematic of the autophagy pathway with the involvement of the Beclin 1-Vps34 class III PI(3)K complexes identified. (hep.com.cn)
  • Fig.3 Currently available structural information of the Atg14L-containing, autophagic Beclin 1-Vps34 class III PI(3)K complex I (PI3KC3-C1). (hep.com.cn)
  • 10.1007/s00125-016-3942-3 ) contains peer-reviewed but unedited supplementary material, which is available to authorised users. (springer.com)