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| Pik3r1SummaryGene Symbol: Pik3r1 Description: phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) Alias: AA414921, C530050K14, PI3K, p50alpha, p55alpha, p85alpha, PI3-kinase regulatory subunit alpha, PI3-kinase subunit p85-alpha, PI3K regulatory subunit alpha, phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha, phosphatidylinositol 3-kinase regulatory subunit alpha, ptdIns-3-kinase regulatory subunit alpha, ptdIns-3-kinase regulatory subunit p85-alpha Species: mouse Top Publications
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Publications
Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cellsD Fang
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
Nat Immunol 2:870-5. 2001..The p85 regulatory subunit of phosphatidylinositol 3 kinase (PI3K) was identified as a substrate for Cbl-b...
CD86 stimulation on a B cell activates the phosphatidylinositol 3-kinase/Akt and phospholipase C gamma 2/protein kinase C alpha beta signaling pathwaysNicholas W Kin
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA
J Immunol 176:6727-35. 2006..In this study, we show that CD86 stimulation on an activated B cell increases the activity of PI3K and the phosphorylation of phosphoinositide-dependent kinase 1, Akt, and IkappaB kinase alphabeta...
Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimersBarbara Geering
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, United Kingdom
Proc Natl Acad Sci U S A 104:7809-14. 2007..p110beta, or p110delta) bound to any of five distinct regulatory subunits (p85alpha, p85beta, p55gamma, p55alpha, and p50alpha, collectively referred to as "p85s")...
p85 Associates with unphosphorylated PTEN and the PTEN-associated complexRosalia Rabinovsky
Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
Mol Cell Biol 29:5377-88. 2009..D3 position of phosphoinositide-3,4,5-trisphosphate, thereby negatively regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway...
Colony-stimulating factor-1 requires PI3-kinase-mediated metabolism for proliferation and survival in myeloid cellsA W M Lee
Department of Pharmacology, University of Michigan Medical School, 1150W Medical Center Dr, Ann Arbor, MI 48109, USA
Cell Death Differ 13:1900-14. 2006..This study identifies robust PI3-kinase activation as essential for optimal CSF-1-mediated mitogenesis in myeloid cells, in part through regulation of HKII and support of glycolysis...
Hyperactivation of p21ras and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functionsFeng Chun Yang
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
J Clin Invest 116:2880-91. 2006..Intercrossing Nf1(+/-) mice and mice deficient in class 1(A) PI3K (p85alpha) restored elevated PI3K activity and Nf1(+/-) osteoclast functions to WT levels...
Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinaseY Terauchi
Department of Internal Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Japan
Nat Genet 21:230-5. 1999..the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5)...
A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein responseJonathon N Winnay
Section on Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
Nat Med 16:438-45. 2010..of insulin, is composed of a catalytic (p110alpha or p110beta) and regulatory (p85alphaalpha, p85betaalpha or p55alpha) subunit...
The monocyte chemoattractant protein-1/CCR2 loop, inducible by TGF-beta, increases podocyte motility and albumin permeabilityEun Young Lee
Division of Nephrology Hypertension, Northwestern University, Chicago, Illinois 60611, USA
Am J Physiol Renal Physiol 297:F85-94. 2009..In conclusion, this is the first description that TGF-beta signaling through PI3K induces the podocyte expression of MCP-1 that can then operate via CCR2 to increase cellular migration and alter ..
T cell Ig and mucin domain-1-mediated T cell activation requires recruitment and activation of phosphoinositide 3-kinaseAnjali J de Souza
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
J Immunol 180:6518-26. 2008..Tim-1 becomes phosphorylated in a lck-dependent manner, whereupon it can directly recruit p85 adaptor subunits of PI3K. This results in PI3K activation, which is required for Tim-1 function...
Structure of lipid kinase p110β/p85β elucidates an unusual SH2-domain-mediated inhibitory mechanismXuxiao Zhang
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
Mol Cell 41:567-78. 2011..This contrasts with the nSH2 where the pY-binding site itself forms the inhibitory contact. This establishes an unusual mechanism by which p85 SH2 domains contribute to RTK signaling specificities...
Competitive displacement of phosphoinositide 3-kinase from beta-adrenergic receptor kinase-1 improves postinfarction adverse myocardial remodelingAntonio Curcio
Dept of Medicine, Cell Biology, and Molecular Genetics, Duke Univ Medical Center, DUMC 3104, Durham, NC 27710, USA
Am J Physiol Heart Circ Physiol 291:H1754-60. 2006..studies have shown that overexpression of the phosphoinositide kinase (PIK) domain of phosphoinositide 3-kinase (PI3K), prevents beta-AR downregulation and enhances adrenergic agonist responsiveness by inhibiting the targeting of ..
Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complexYun Zhong
1 Laboratory of Molecular Biology, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10065, USA 2 These authors contributed equally to the work
Nat Cell Biol 11:468-76. 2009..We hypothesize that by forming distinct protein complexes, Beclin 1 and its binding proteins orchestrate the precise function of the class III PI(3)K in regulating autophagy at multiple steps...
Rescuing 3T3-L1 adipocytes from insulin resistance induced by stimulation of Akt-mammalian target of rapamycin/p70 S6 kinase (S6K1) pathway and serine phosphorylation of insulin receptor substrate-1: effect of reduced expression of p85alpha subunit of phoRebecca Adochio
Department of Veterans Affairs, University of Colorado Denver, Aurora, Colorado 80045, USA
Endocrinology 150:1165-73. 2009..We then reduced expression of the PI 3-kinase regulatory subunit, p85alpha, or expression of S6K1 kinase using small interfering RNA transfections, which led to a reduction in p85alpha ..
A novel T608R missense mutation in insulin receptor substrate-1 identified in a subject with type 2 diabetes impairs metabolic insulin signalingDiana L Esposito
Department of Oncology and Neurosciences, Section of Molecular Pathology, University Gabriele D Annunzio, 66013 Chieti, Italy
J Clin Endocrinol Metab 88:1468-75. 2003..We conclude that a naturally occurring substitution of Arg for Thr(608) in IRS-1 is a rare human mutation that may contribute to insulin resistance by impairing metabolic signaling through PI 3-kinase-dependent pathways...
Activation of phosphatidylinositol-3 kinase regulates pancreatic duodenal homeobox-1 in duct cells during pancreatic regenerationHiroaki Watanabe
Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555 0526, USA
Pancreas 36:153-9. 2008The purpose of our study was to determine whether the phosphatidylinositol 3-kinase (PI3K)/Akt pathway contributes to expression of pancreatic duodenal homeobox-1 (PDX-1) in duct cells and the cell differentiation during pancreatic ..
Role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangementSaskia M Brachmann
Beth Israel Hospital, NRB, Division of Signal Transduction, Department of Systems Biology, 10th Floor, 330 Brookline, MA 02215, USA
Mol Cell Biol 25:2593-606. 2005..Although embryonic development is not impaired in mice lacking all isoforms of the p85alpha gene (p85alpha-/- p55alpha-/- p50alpha-/-) or in mice lacking the p85beta gene (p85beta-/-) (D. A. Fruman, F. Mauvais-Jarvis, D. A...
Phosphoinositide 3-kinase signaling to Akt promotes keratinocyte differentiation versus deathEnzo Calautti
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
J Biol Chem 280:32856-65. 2005..We show here that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated at early stages of mouse keratinocyte differentiation both in culture and in the intact ..
The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complexJi Luo
Department of Systems Biology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
J Cell Biol 170:455-64. 2005..To further understand the role of p85, we examined IGF-1-dependent translocation of p85alpha by using a green fluorescence protein (GFP)-tagged p85alpha (EGFP-p85alpha)...
Insulin-stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5Xiong Su
Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 281:27982-90. 2006..of PKB/Akt activation was because of the impaired interaction between insulin receptor substrate 1 and the p85alpha subunit of phosphatidylinositol 3-kinase...
Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulationLazaros C Foukas
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
Nature 441:366-70. 2006..These findings demonstrate a critical role for p110alpha in growth factor and metabolic signalling and also suggest an explanation for selective mutation or overexpression of p110alpha in a variety of cancers...
Protein kinase C-delta and phosphatidylinositol 3-kinase/Akt activate mammalian target of rapamycin to modulate NF-kappaB activation and intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cellsMohd Minhajuddin
Department of Pediatrics Neonatology, Lung Biology and Disease Program, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Biol Chem 284:4052-61. 2009..was defective in embryonic fibroblasts from mice with targeted disruption of PKC-delta (Pkc-delta(-)(/)(-)), p85alpha and p85beta subunits of the PI3K (p85alpha(-)(/)(-)beta(-)(/)(-)), or Akt1 and Akt2 (Akt1(-)(/)(-)2(-)(/)(-))...
Role of the docking protein Gab2 in beta(1)-integrin signaling pathway-mediated hematopoietic cell adhesion and migrationWen Mei Yu
Department of Hematopoiesis, Jerome H Holland Laboratory for the Biomedical Sciences, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855, USA
Blood 99:2351-9. 2002..Taken together, these results suggest an important signaling role for Gab2 in regulating hematopoietic cell adhesion and migration...
Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alphaD A Fruman
Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Science 283:393-7. 1999..The mouse gene encoding the PI3K adapter subunit p85alpha and its splice variants p55alpha and p50alpha was disrupted. Most p85alpha-p55alpha-p50alpha-/- mice die within days after birth...
Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol 3-kinase (PI3-kinase), and concomitantly PI3-kinase activation via JAK2 kinaseT Yamauchi
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113, Japan
J Biol Chem 273:15719-26. 1998..Taken together, the role of IRS-1, -2, and -3 in GH and PRL signalings appears to be phosphorylated by JAK2, thereby providing docking sites for p85 PI3-kinase and activating PI3-kinase and its downstream biological effects...
Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alphaD A Fruman
Division of Signal Transduction, Beth Israel Deaconess Medical Center Boston, Massachusetts, USA
Nat Genet 26:379-82. 2000..The gene Pik3r1 encodes three proteins (p85 alpha, p55 alpha and p50 alpha) that serve as regulatory subunits of class IA Pi3ks (..
The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocationSang Won Park
Division of Endocrinology, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA
Nat Med 16:429-37. 2010..Here, we show that the regulatory subunits of phosphotidyl inositol 3-kinase (PI3K), p85alpha (encoded by Pik3r1) and p85beta (encoded by Pik3r2) form heterodimers that are disrupted by insulin treatment...
Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signalingKohjiro Ueki
Research Division, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA
J Biol Chem 278:48453-66. 2003..regulatory isoforms, p85 alpha and p85 beta, we have established brown adipose cell lines with disruption of the Pik3r1 or Pik3r2 gene...
Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetesFranck Mauvais-Jarvis
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
J Clin Invest 109:141-9. 2002..The major regulatory subunits of PI 3-kinase, p85alpha and its splice variants, are encoded by the Pik3r1 gene...
Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survivalKohjiro Ueki
Research Division, Joslin Diabetes Center, Harvard Medical School Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Mol Cell Biol 22:965-77. 2002..of a p110 catalytic subunit and a regulatory subunit, the most common family of which is derived from the p85alpha gene (Pik3r1)...
p50alpha/p55alpha phosphoinositide 3-kinase knockout mice exhibit enhanced insulin sensitivityDong Chen
Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
Mol Cell Biol 24:320-9. 2004..tissues such as fat, muscle, and liver express the splice variants of the pik3r1 gene, p50alpha and p55alpha. To define the role of these variants, we have created mice with a deletion of p50alpha and p55alpha by using ..
Nf1-/- Schwann cell-conditioned medium modulates mast cell degranulation by c-Kit-mediated hyperactivation of phosphatidylinositol 3-kinaseShi Chen
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Am J Pathol 177:3125-32. 2010..as well as pharmacological agents to link the hyperactivation of the p21(Ras)-phosphatidylinositol 3-kinase (PI3K) pathway to the increased degranulation of Nf1(+/-) mast cells both in vitro and in vivo...
The PI3K-Akt pathway promotes microtubule stabilization in migrating fibroblastsKeisuke Onishi
Institute of Molecular and Cellular Biosciences, University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 0032, Japan
Genes Cells 12:535-46. 2007..Here we show that the PI3K-Akt signaling pathway plays a pivotal role in growth factor regulation of microtubule stability...
TIMP-3 and Phosphatidylinositol 3-kinase genes were found to be related to the progression of colon cancer in a comparison of pneumoperitoneum and laparotomy in a murine modelFumiaki Tanaka
Division of Molecular and Surgical Oncology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874 0838, Japan
Surg Today 37:220-5. 2007..However, no basic and molecular-biological examinations have yet to elucidate the mechanisms of such an improved outcome...
Class IA phosphatidylinositol 3-kinase in pancreatic β cells controls insulin secretion by multiple mechanismsKazuma Kaneko
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113 8655, Japan
Cell Metab 12:619-32. 2010..Inhibition of class IA phosphatidylinositol 3-kinase (PI3K), using a mouse model lacking the pik3r1 gene specifically in β cells and the pik3r2 gene systemically (βDKO mouse), results in glucose intolerance and ..
Tyrosine kinase Btk regulates E-selectin-mediated integrin activation and neutrophil recruitment by controlling phospholipase C (PLC) gamma2 and PI3Kgamma pathwaysHelena Mueller
Department of Anesthesiology and Intensive Care Medicine, University of Munster, 48149 Munster, Germany
Blood 115:3118-27. 2010..the signaling pathway downstream of Syk divides into a phospholipase C (PLC) gamma2- and phosphoinositide 3-kinase (PI3K) gamma-dependent pathway...
Dynamics of the phosphoinositide 3-kinase p110δ interaction with p85α and membranes reveals aspects of regulation distinct from p110αJohn E Burke
Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
Structure 19:1127-37. 2011..DXMS identified regions decreasing exposure at membranes and also regions gaining exposure, indicating loosening of interactions within the heterodimer at membranes...
Inhibition of PI3K binding to activators by serine phosphorylation of PI3K regulatory subunit p85alpha Src homology-2 domainsJennifer Y Lee
Division of Signal Transduction, Cancer Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 108:14157-62. 2011..The p85 regulatory subunit of PI3K contains Src homology-2 (SH2) domains that mediate binding to tyrosine-phosphorylated receptors or adaptor proteins ..
Balanced interactions between Lyn, the p85alpha regulatory subunit of class I(A) phosphatidylinositol-3-kinase, and SHIP are essential for mast cell growth and maturationPeilin Ma
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W Walnut Street, Indianapolis, IN 46202, USA
Mol Cell Biol 31:4052-62. 2011..forms of these receptors lacking the binding sites for Src family kinases (SFKs) and phosphatidylinositol-3-kinase (PI3K) suggest a role for these signaling molecules in regulating growth and survival, how complete loss of these ..
Appl1 is dispensable for Akt signaling in vivo and mouse T-cell developmentYinfei Tan
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
Genesis 48:531-9. 2010..that participates in cell signaling by interacting with various signaling molecules including Akt, PI3-kinase (PI3K), Rab5, adiponectin receptor, and TrkA...
TLR4/MyD88/PI3K interactions regulate TLR4 signalingMichelle H W Laird
University of Maryland, Baltimore, 660 W Redwood Street, Room 324, Baltimore, MD 21201, USA
J Leukoc Biol 85:966-77. 2009..TLR4-mediated signaling also leads to rapid activation of PI3K, one of a family of kinases involved in regulation of cell growth, apoptosis, and motility...
PI3K signaling in glioma--animal models and therapeutic challengesChristine K Cheng
Department of Neurology, University of California, San Francisco, CA 94143, USA
Brain Pathol 19:112-20. 2009The PI3 kinase (PI3K) family plays a complex role in cell biology and metabolism...
Regulation of microtubule nucleation from membranes by complexes of membrane-bound gamma-tubulin with Fyn kinase and phosphoinositide 3-kinaseLibor Macurek
Department of Biology of Cytoskeleton, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic
Biochem J 416:421-30. 2008..Furthermore, in vitro kinase assays showed that p85alpha (regulatory p85alpha subunit of PI3K) serves as a Fyn substrate...
Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cellsMasashi Ohtani
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan
Blood 112:635-43. 2008Phosphoinositide 3-kinase (PI3K) negatively regulates Toll-like receptor (TLR)-mediated interleukin-12 (IL-12) expression in dendritic cells (DCs)...
Toll-like receptor 2- and MyD88-dependent phosphatidylinositol 3-kinase and Rac1 activation facilitates the phagocytosis of Listeria monocytogenes by murine macrophagesYanna Shen
Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshidakonoe cho, Sakyo ku, Kyoto 606 8501, Japan
Infect Immun 78:2857-67. 2010..The efficiency of phagocytosis was suppressed by inhibitors of phosphatidylinositol 3-kinase (PI3K) and the small Rho GTPases but not by cycloheximide...
Disrupted RabGAP function of the p85 subunit of phosphatidylinositol 3-kinase results in cell transformationM Dean Chamberlain
Cancer Research Unit, Health Research Division, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan S7N 4H4, Canada
J Biol Chem 283:15861-8. 2008..The p85alpha subunit of phosphatidylinositol 3-kinase has GTPase-activating protein activity toward Rab5 and Rab4, an activity ..
The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitmentMargaret I Arbuckle
Centre for Neuroregeneration, The University of Edinburgh, Institute of Immunology and Infection, Ashworth Buildings, Kings Buildings, Edinburgh EH9 3JT, UK
EMBO Rep 11:473-8. 2010..These results show that different types of behavioural plasticity are mediated by specific domains of PSD95 and suggest novel therapeutic avenues for reducing inflammatory pain...
c-Src is required for tropomyosin receptor kinase C (TrkC)-induced activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathwayWook Jin
Laboratory of Cell Regulation and Carcinogenesis, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406 840, Korea
J Biol Chem 283:1391-400. 2008..major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival...
Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse beta-cellsSubbiah Pugazhenthi
Department of Medicine, University of Colorado at Denver and Health Sciences Center, P O Box 6511, Mail Stop 8106, Aurora, CO 80045, USA
Am J Physiol Endocrinol Metab 293:E645-55. 2007..Our observations suggest that demethoxy curcuminoids could be used to induce a cellular defense mechanism in beta-cells under conditions of stress as seen in diabetes...
A PI3K activity-independent function of p85 regulatory subunit in control of mammalian cytokinesisZaira García
Department of Immunology and Oncology, Centro Nacional de Biotecnologia CSIC, Universidad Autonoma de Madrid, Cantoblanco, Madrid, Spain
EMBO J 25:4740-51. 2006..We studied the role of p85/p110 phosphoinositide kinase (PI3K) in mammalian cytokinesis. Deletion of the p85alpha regulatory subunit induced cell accumulation in telophase and appearance of binucleated cells, whereas inhibition ..
Interleukin-7 induces the association of phosphatidylinositol 3-kinase with the alpha chain of the interleukin-7 receptorA R Venkitaraman
Medical Research Council, Laboratory of Molecular Biology, Cambridge, GB
Eur J Immunol 24:2168-74. 1994..PtdIns 3-kinase may, therefore, play a unique and important role in the biological response to IL-7...
Functional p85alpha gene is required for normal murine fetal erythropoiesisHannah Huddleston
Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W Walnut St, R4 470, Indianapolis, IN 46202, USA
Blood 102:142-5. 2003..However, when class IA PI-3 kinase-deficient mice were generated by a targeted deletion of the p85alpha regulatory subunit, fetal erythropoiesis was reportedly unaffected...
Receptor-specific regulation of phosphatidylinositol 3'-kinase activation by the protein tyrosine phosphatase Shp2Si Qing Zhang
Cancer Biology Program, Division of Hematology Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02115, USA
Mol Cell Biol 22:4062-72. 2002..that the protein tyrosine phosphatase Shp2 regulates the strength and duration of phosphatidylinositol 3'-kinase (PI3K) activation in the epidermal growth factor (EGF) receptor signaling pathway...
BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activationT Okada
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan
Immunity 13:817-27. 2000..Here, we report the identification of a novel B cell adaptor for phosphoinositide 3-kinase (PI3K), termed BCAP...
Vav-dependent and vav-independent phosphatidylinositol 3-kinase activation in murine B cells determined by the nature of the stimulusElena Vigorito
Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, Babraham Institute, Babraham, Cambridge, United Kingdom
J Immunol 173:3209-14. 2004..The p85alpha and p110delta subunits of PI3K both participate in anti-IgM and mIg/CD19 coligation-induced Ca(2+) flux, although ..
PI3K and Btk differentially regulate B cell antigen receptor-mediated signal transductionHarumi Suzuki
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160 8582, Japan
Nat Immunol 4:280-6. 2003Phosphoinositide-3 kinase (PI3K) is thought to activate the tyrosine kinase Btk...
Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85alphaAmber C Donahue
Center for Immunology and Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA
Int Immunol 16:1789-98. 2004..Mice lacking p85alpha, the predominant PI3K regulatory isoform, exhibit defects in B cell development and activation that are grossly ..
Different effects of insulin and platelet-derived growth factor on phosphatidylinositol 3-kinase at the subcellular level in 3T3-L1 adipocytes. A possible explanation for their specific effects on glucose transportJ M Ricort
INSERM U 145, Faculte de Medecine, Nice, France
Eur J Biochem 239:17-22. 1996....
RANKL-induced down-regulation of CX3CR1 via PI3K/Akt signaling pathway suppresses Fractalkine/CX3CL1-induced cellular responses in RAW264.7 cellsYurika Saitoh
Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930 0194, Japan
Biochem Biophys Res Commun 364:417-22. 2007..Inhibitors of phosphatidylinositol 3-kinase (PI3K) and Akt, but not mitogen-activated protein kinases, restored the RANKL-induced reduction of CX3CR1 mRNA...
Class IA phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophyJi Luo
Division of Systems Biology, Harvard Medical School, Beth Israel Deaconess Medical Center, 77 Avenue Louis Pasteur, 10th Floor, Boston, MA 02115, USA
Mol Cell Biol 25:9491-502. 2005..of dominant negative and constitutively active proteins, we generated mice with muscle-specific deletion of the p85alpha regulatory subunit and germ line deletion of the p85beta regulatory subunit of class I(A) PI3K...
BCR targets cyclin D2 via Btk and the p85alpha subunit of PI3-K to induce cell cycle progression in primary mouse B cellsJanet Glassford
Cancer Research UK Labs and Section of Cancer Cell Biology, Department of Cancer Medicine, Imperial College School of Medicine at Hammersmith Hospital, Londom, UK
Oncogene 22:2248-59. 2003The p85alpha subunit of PI3-K and Btk are two crucial components of the B-cell receptor (BCR) signalling pathway...
Thrombopoietin (TPO) induces c-myc expression through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKCzeta or mTOR in TPO-dependent cell lines and primary megakaryocytesSupantitra Chanprasert
Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
Cell Signal 18:1212-8. 2006..TPO signals through the Jak-STAT, Ras-Raf-MAPK, and PI3K pathways, and promotes survival, proliferation, and polyploidization in megakaryocytes...
Distinct roles of phosphoinositide-3 kinase and phospholipase Cgamma2 in B-cell receptor-mediated signal transductionXuezhi Dai
Blood Research Institute, 8727 Watertown Plank Rd, Milwaukee, WI 53226, USA
Mol Cell Biol 26:88-99. 2006During B-cell receptor (BCR) signaling, phosphoinositide-3 kinase (PI3K) is thought to function upstream of phospholipase Cgamma2 (PLCgamma2)...
Role of TNF receptor-associated factor 3 in the CD40 signaling by production of reactive oxygen species through association with p40phox, a cytosolic subunit of nicotinamide adenine dinucleotide phosphate oxidaseYun Jung Ha
Division of Molecular Life Sciences and Center for Cell Signaling Research, College of Natural Sciences, Ewha Womans University, 11 1 Daehyun Dong, Seodaemun gu, Seoul 120 750, Korea
J Immunol 172:231-9. 2004..Collectively, these data suggest that the CD40-induced ROS production by NADPH oxidase in WEHI 231 requires the role of TRAF3, as well as activities of PI3-K and Rac1...
Role of the liver in glucose homeostasis in PI 3-kinase p85alpha-deficient miceKazutaka Aoki
Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, 3 9 Fukuura, Kanazawa Ku, Yokohama 236 0004, Japan
Am J Physiol Endocrinol Metab 296:E842-53. 2009..In the livers of p85alpha-deficient mice, p50alpha played a compensatory role in insulin-stimulated PI3K activation by binding to insulin receptor substrate (IRS)-1/..
An involvement of BDNF and PI3-K/Akt in the anti-apoptotic effect of memantine on staurosporine-evoked cell death in primary cortical neuronsD Jantas
Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31 343 Krakow, Poland
Apoptosis 14:900-12. 2009..e. ERK1/2, JNK and GSK3-beta. The obtained data suggest an NMDAR-independent action of memantine in attenuation of neuronal apoptosis and point to the engagement of BDNF and PI3-K/Akt pathway in these processes...
Fibroblast growth factor 2-induced cytoplasmic asparaginyl-tRNA synthetase promotes survival of osteoblasts by regulating anti-apoptotic PI3K/Akt signalingSu Jin Park
Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, Seoul, Republic of Korea
Bone 45:994-1003. 2009..In addition, NARS-induced protection against apoptosis was abolished by the treatment of PI3K inhibitors, wortmannin and LY294002...
Effect of spontaneous gestational diabetes on fetal and postnatal hepatic insulin resistance in Lepr(db/+) miceHiroshi Yamashita
Department of Pediatric, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
Pediatr Res 53:411-8. 2003....
Mesothelin inhibits paclitaxel-induced apoptosis through the PI3K pathwayMing Cheng Chang
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan
Biochem J 424:449-58. 2009..Furthermore, mesothelin-treated cells revealed rapid tyrosine phosphorylation of the p85 subunit of PI3K (phosphoinositide 3-kinase) and ERK (extracellular-signal-regulated kinase) 1/2 for enhancing MAPK (mitogen-..
The gene that encodes the phosphatidylinositol-3 kinase regulatory subunit (p85 alpha) maps to chromosome 13 in the mouseJ Hoyle
Department of Biochemistry and Molecular Genetics, St. Mary's Hospital Medical School, Imperial College, London, United Kingdom
Genomics 24:400-2. 1994
Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinaseD D Schlaepfer
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186
Nature 372:786-91. 1994..Phosphorylation of FAK at Tyr 925 upon fibronectin stimulation creates an SH2-binding site for GRB2 which may link integrin engagement to the activation of the Ras/MAPK signal transduction pathway...
The GTPase dynamin binds to and is activated by a subset of SH3 domainsI Gout
Ludwig Institute for Cancer Research, London, England
Cell 75:25-36. 1993....
Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinaseY W Fridell
Lineberger Comprehensive Cancer Center, Department of Pharmacology, University of North Carolina at Chapel Hill 27599 7295, USA
Mol Cell Biol 16:135-45. 1996..Furthermore, our data suggest that the GAS6-Axl interaction does not induce mitogenesis and that its exact role remains to be determined...
Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migrationN Jones
Division of Cancer Biology Research, Sunnybrook and Women s College Health Sciences Centre, University of Toronto, Toronto, Ontario M4N 3M5
J Biol Chem 274:30896-905. 1999..Taken together, these results demonstrate that Angiopoietin-1-induced signaling from the Tek receptor is mediated by a multifunctional docking site that is responsible for activation of both cell migration and cell survival pathways...
Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-bK Bachmaier
Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada
Nature 403:211-6. 2000..Cbl-b is thus a key regulator of activation thresholds in mature lymphocytes and immunological tolerance and autoimmunity...
Identification of two chromosomal loci determining glucose intolerance in a C57BL/6 mouse strainT Kayo
Department of Hygiene, Akita University School of Medicine, Japan
Comp Med 50:296-302. 2000..05) at 10, 20, and 30 minutes during the intraperitoneal glucose tolerance test (IPGTT: 1.5 g glucose/kg of body weight)...
Phosphatidylinositol 3-kinase/Akt plays a part in tumor necrosis factor-alpha-induced interleukin-6 synthesis in osteoblastsS Takai
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
Horm Metab Res 38:563-9. 2006..These results strongly suggest that PI3-kinase/Akt plays a role in the TNF-alpha-stimulated IL-6 synthesis mainly independent of p44/p42 MAP kinase in osteoblasts...
Heat shock cognate protein 70 is essential for Akt signaling in endothelial functionMasayuki Shiota
Department of Pharmacology, Osaka City University Medical School, 1 4 3 Asahi machi, Abeno Ku, Osaka 545 8585, Japan
Arterioscler Thromb Vasc Biol 30:491-7. 2010..Herein, we investigate the role of Hsp70s, including heat shock cognate protein 70 (Hsc70), which is constitutively expressed in nonstressed cells (ie, ECs)...
Oncogenic H-Ras and PI3K signaling can inhibit E-cadherin-dependent apoptosis and promote cell survival after photodynamic therapy in mouse keratinocytesJesus Espada
Instituto de Investigaciones Biomedicas Alberto Sols, CSIC Departamento de Bioquímica, Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain
J Cell Physiol 219:84-93. 2009..situation was observed in cells showing constitutive activation of the p110 alpha catalytic subunit of class IA PI3K. This protective effect is associated with beta-catenin-dependent transcription and with activation of survival ..
Enkurin is a novel calmodulin and TRPC channel binding protein in spermKeith A Sutton
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA
Dev Biol 274:426-35. 2004..We suggest that enkurin is an adaptor that functions to localize a Ca2+ sensitive signal transduction machinery in sperm to a Ca2+-permeable ion channel...
Increased P85alpha is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excessLinda A Barbour
Department of Medicine, University Colorado Health Sciences Center, Denver, 80262, USA
J Biol Chem 280:37489-94. 2005..Herein, using transgenic mice bearing deletions in p85alpha, p85beta, or insulin-like growth factor-1, we provide novel evidence suggesting that overexpression of p85alpha ..
Learning deficits and agenesis of synapses and myelinated axons in phosphoinositide-3 kinase-deficient miceChihiro Tohda
Divisions of Biofunctional Evaluation, Research Center for Ethnomedicine, Institute of Natural Medicine, University of Toyama, Toyama, Japan
Neurosignals 15:293-306. 2006..Knockout mice lacking the p85alpha regulatory subunit of PI3K (p85alpha-/- mice) significantly showed learning deficits, restlessness and motivation ..
Effects of dietary calorie restriction or exercise on the PI3K and Ras signaling pathways in the skin of miceLinglin Xie
Department of Human Nutrition and Statistics, Kansas State University, Manhattan, Kansas 66506, USA
J Biol Chem 282:28025-35. 2007..of weight loss by increasing physical activity or decreasing calorie intake on tumor promoter-induced Ras-MAPK and PI3K-Akt pathways...
Phosphoinositide 3-kinase accelerates postoperative tumor growth by inhibiting apoptosis and enhancing resistance to chemotherapy-induced apoptosis. Novel role for an old enemyJ Calvin Coffey
Department of Surgery, Cork University Hospital, Wilton, Cork, Munster, Ireland
J Biol Chem 280:20968-77. 2005..This identified an increase and reduction in the expression of p110gamma and p85alpha class Ia phosphoinositide 3-kinase (PI3K) subunits in recurrent tumor epithelia...
Phosphoinositide 3-kinase, Src, and Akt modulate acute ventilation-induced vascular permeability increases in mouse lungsTakashige Miyahara
Department of Physiology, University of South Alabama, Mobile, Alabama 36688, USA
Am J Physiol Lung Cell Mol Physiol 293:L11-21. 2007To determine the role of phosphoinositide 3-OH kinase (PI3K) pathways in the acute vascular permeability increase associated with ventilator-induced lung injury, we ventilated isolated perfused lungs and intact C57BL/6 mice with low and ..
Sjögren's syndrome-like disease in mice with T cells lacking class 1A phosphoinositide-3-kinaseJean S Oak
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697 3900, USA
Proc Natl Acad Sci U S A 103:16882-7. 2006..In addition, the mouse model described here represents a tool to study the pathogenesis and treatment of SS...
Active Ras-induced effects on skeletal myoblast differentiation and apoptosis are independent of constitutive PI3-kinase activityM Karasarides
Department of Cell Biology, Learner Research Institute, Cleveland Clinic Foundation, OH 44195, USA
Cell Biol Int 30:308-18. 2006..Thus, our data suggest that a pathway distinct from those that signals through MAPK, NFkappaB or PI3-kinase is responsible for the impaired differentiation and apoptosis in 23A2 skeletal myoblasts expressing constitutively active Ras...
Hypothalamic phosphatidylinositol 3-kinase pathway of leptin signaling is impaired during the development of diet-induced obesity in FVB/N miceAnantha S Metlakunta
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
Endocrinology 149:1121-8. 2008Phosphatidylinositol 3-kinase (PI3K) pathway of leptin signaling plays an important role in transducing leptin action in the hypothalamus...
Yes and PI3K bind CD95 to signal invasion of glioblastomaSusanne Kleber
Molecular Neurobiology Group, German Cancer Research Center DKFZ, INF 581, 69120 Heidelberg, Germany
Cancer Cell 13:235-48. 2008..Our results uncover CD95 as an activator of PI3K and, most importantly, as a crucial trigger of basal invasion of glioblastoma in vivo.
LIME, a novel transmembrane adaptor protein, associates with p56lck and mediates T cell activationEun Mi Hur
Div of Molecular Life Science, Ewha Woman s University, 11 1 Daehyundong, Seodaemungu, 120 750 Seoul, Korea
J Exp Med 198:1463-73. 2003..Our data collectively show that LIME is a raft-associated transmembrane adaptor protein linking TCR stimuli to downstream signaling pathways via associations with Lck...
Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin neurons in miceJennifer W Hill
Division of Hypothalamic Research, Department of Internal Medicine and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Clin Invest 118:1796-805. 2008..It has been proposed that leptin action requires PI3K activity...
[Role of jak/STAT3 and PI3-K/Akt pathways in liver injury and regeneration]Michitaka Ozaki
Department of Molecular Surgery, Hokkaido University School of Medicine, Sapporo, Japan
Seikagaku 80:399-408. 2008
Induction of cyclooxygenase-2 in macrophages by catalase: role of NF-kappaB and PI3K signaling pathwaysByeong Churl Jang
Chronic Disease Research Center and Institute for Medical Science, Keimyung University School of Medicine, 194 Dongsan dong, Jung Gu, Daegu 700 712, South Korea
Biochem Biophys Res Commun 316:398-406. 2004..Catalase also induced activation of NF-kappaB, PI3K, ERKs, p38s, or JNKs...
The p85alpha subunit of phosphatidylinositol 3'-kinase binds to and stimulates the GTPase activity of Rab proteinsM Dean Chamberlain
Cancer Research Unit, Health Research Division, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan S7N 4H4, Canada
J Biol Chem 279:48607-14. 2004..The p85alpha subunit of phosphatidylinositol 3'-kinase contains a BH domain with sequence homology to GTPase activating ..
Frontline: The p85alpha isoform of phosphoinositide 3-kinase is essential for a subset of B cell receptor-initiated signaling responsesKristen L Hess
Center for Immunology, Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA
Eur J Immunol 34:2968-76. 2004..B cell receptor (BCR)-driven proliferation is completely blocked either in cells lacking the p85alpha regulatory isoform of PI3K or in wild-type cells treated with pharmacological PI3K inhibitors...
Control of axonal growth and regeneration of sensory neurons by the p110delta PI 3-kinaseBritta J Eickholt
Medical Research Council Centre for Developmental Neurobiology, King s College London, London, United Kingdom
PLoS ONE 2:e869. 2007The expression and function of the 8 distinct catalytic isoforms of PI 3-kinase (PI3K) in the nervous system are unknown...
Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKClambda/zetaCullen M Taniguchi
Cellular and Molecular Physiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
Cell Metab 3:343-53. 2006..of hepatic function, we ablated the expression of both major regulatory subunits of PI3K by crossing mice lacking Pik3r1 in liver with Pik3r2 null mice, creating liver-specific double knockout mice (L-p85DKO)...
Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL+ leukemia cellsMichael G Kharas
Department of Molecular Biology and Biochemistry, Center for Immunology, University of California, Irvine, Irvine, California, USA
J Clin Invest 118:3038-50. 2008..Using a murine model of Ph+ pre-B-ALL, we found that deletion of both Pik3r1 and Pik3r2, genes encoding class IA PI3K regulatory isoforms, severely impaired transformation...
LIME acts as a transmembrane adapter mediating BCR-dependent B-cell activationEunseon Ahn
Division of Molecular Life Science, Ewha Womans University, 11 1, Daehyun dong, Seodaemoon Gu, Seoul, 120 750, Korea
Blood 107:1521-7. 2006..Upon BCR cross-linking, LIME was tyrosine phosphorylated by Lyn and associated with Lyn, Grb2, PLC-gamma2, and PI3K. Reduction of LIME expression by the introduction of siRNA resulted in the disruption of BCR-mediated activation of ..
TLR4/CD14-mediated PI3K activation is an essential component of interferon-dependent VSV resistance in macrophagesGernot Schabbauer
Department for Vascular Biology, Center for Biomolecular Medicine and Pharmacology, Medical University Vienna, Schwarzspanierstrasse 17, Vienna, Austria
Mol Immunol 45:2790-6. 2008Phosphatidylinositol-3-phosphate kinase (PI3K) has been reported to exhibit anti-inflammatory roles as a negative modulator of the NF-kappaB pathway (MyD88- and Mal-dependent) triggered upon Toll-like receptor (TLR)4 activation by ..
Research Grants
- Dietary supplementation with glucan enhances immune fnDavid Williams; Fiscal Year: 2002..At the successful conclusion of this research e will have established what, if any, effect dietary supplementation with glucan has on modulating immunocompetence arid whether oral glucans will increase resistance to infectious diseases. ..
- Light Activation of Retinal Insulin Receptor SignalingRAJU RAJALA; Fiscal Year: 2007..The biological implications extend to the cause and treatment of a number of retinal degenerative diseases. ..
- Light Activation of Retinal Insulin Receptor SignalingRAJU RAJALA; Fiscal Year: 2009..The biological implications extend to the cause and treatment of a number of retinal degenerative diseases. ..
- AMELIORATION OF SEPSIS BY MACROPHAGE ACTIVATIONDavid Williams; Fiscal Year: 2009..The phosphoinsitide 3-kinases/Akt (PI3K/Akt) is a conserved family of signal transduction enzymes which are involved in regulating cellular proliferation ..
- AMELIORATION OF SEPSIS BY MACROPHAGE ACTIVATIONDavid Williams; Fiscal Year: 2009..The phosphoinsitide 3-kinases/Akt (PI3K/Akt) is a conserved family of signal transduction enzymes which are involved in regulating cellular proliferation ..
- AMELIORATION OF SEPSIS BY MACROPHAGE ACTIVATIONDavid Williams; Fiscal Year: 1999..These data may ultimately lead to the development of better management strategies for patients predisposed to sepsis and septic shock. ..
- INSULIN RECEPTOR SIGNALING IN THE RETINARAJU RAJALA; Fiscal Year: 2002..Recently, we have reported that the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) interacts directly with the insulin receptor-beta subunit (IRb) in retinal rod outer segments (ROS), which leads ..
- AMELIORATION OF SEPSIS BY MACROPHAGE ACTIVATIONDavid Williams; Fiscal Year: 2004..The successful completion of these aims will advance our understanding of the cellular and molecular events associated with sepsis syndrome and may lead to the development of new therapeutics. ..
- Light Activation of Retinal Insulin Receptor SignalingRAJU VS RAJALA; Fiscal Year: 2010..Light-activated IR is subsequently associated with phosphoinositide 3-kinase (PI3K), a cell survival factor, and thus regulates the downstream survival pathway...
