p85

Summary

Gene Symbol: p85
Description: phosphoinositide-3-kinase regulatory subunit 1
Alias: AGM7, GRB1, IMD36, p85, p85-ALPHA, phosphatidylinositol 3-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, polypeptide 1 (p85 alpha), phosphatidylinositol 3-kinase-associated p-85 alpha, phosphoinositide-3-kinase regulatory subunit, phosphoinositide-3-kinase regulatory subunit alpha, phosphoinositide-3-kinase, regulatory subunit 1 (alpha), ptdIns-3-kinase regulatory subunit alpha
Species: human

Top Publications

  1. pmc Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation
    Bijay S Jaiswal
    Department of Molecular Biology, Genentech Inc, South San Francisco, CA 94080, USA
    Cancer Cell 16:463-74. 2009
  2. ncbi Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit
    Nabil Miled
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Science 317:239-42. 2007
  3. doi NKX2-1/TITF1/TTF-1-Induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma
    Tomoya Yamaguchi
    Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Showa Ku, Nagoya 466 8550, Japan
    Cancer Cell 21:348-61. 2012
  4. ncbi Phosphatidylinositol 3-kinase in interleukin 1 signaling. Physical interaction with the interleukin 1 receptor and requirement in NFkappaB and AP-1 activation
    S A Reddy
    Department of Biochemistry and Molecular Biology, Box 117, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 272:29167-73. 1997
  5. pmc Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase
    T Simoncini
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 407:538-41. 2000
  6. pmc HIV-1 Tat promotes Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6-induced angiogenesis and tumorigenesis by regulating PI3K/PTEN/AKT/GSK-3β signaling pathway
    Feng Zhou
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People s Republic of China
    PLoS ONE 8:e53145. 2013
  7. doi Association between phosphatidylinositol 3-kinase regulatory subunit p85alpha Met326Ile genetic polymorphism and colon cancer risk
    Li Li
    Department of Family Medicine Research Division, Case Western Reserve University, Cleveland, OH 44106 7136, USA
    Clin Cancer Res 14:633-7. 2008
  8. pmc Hypoxia up-regulates CD36 expression and function via hypoxia-inducible factor-1- and phosphatidylinositol 3-kinase-dependent mechanisms
    Bupe R Mwaikambo
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 284:26695-707. 2009
  9. pmc PIK3R1 (p85α) is somatically mutated at high frequency in primary endometrial cancer
    Mary E Urick
    Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 71:4061-7. 2011
  10. pmc PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells
    G Castoria
    Dipartimento di Patologia Generale, Facolta di Medicina e Chirurgia, II Universita di Napoli, Via L De Crecchio, 7, 80138 Napoli, Italy
    EMBO J 20:6050-9. 2001

Research Grants

  1. Regulation and Function of hVps34 in Insulin Signaling
    Jonathan M Backer; Fiscal Year: 2010
  2. Non-apoptotic functions of caspases
    STEVEN MILES FRISCH; Fiscal Year: 2012
  3. Role of PI 3-Kinase isoforms in insulin action
    C Ronald Kahn; Fiscal Year: 2013
  4. ANG II AND IGF-1 INTERACTION IN CARDIOVASCULAR TISSUE
    James Sowers; Fiscal Year: 2003
  5. Selective Insulin Resistance- Diabetic Cardiovascular Diseases
    George L King; Fiscal Year: 2013
  6. p85/p110 PI3 Kinase-Structure, function and Physiology
    Jonathan M Backer; Fiscal Year: 2013
  7. P3K, RETROVIRAL ONCOGENE AND HOMOLOG OF PI 3-KINASE
    Peter K Vogt; Fiscal Year: 2013
  8. Myocardial ischemic activation of the Akt pathway
    STEPHEN ARMSTRONG; Fiscal Year: 2007
  9. Novel Function of PI 3-Kinase in Calcium Regulation
    Ching Shih Chen; Fiscal Year: 2004
  10. CD4/CD8 P56LCK AND ASSOCIATED KINASES
    CHRISTOPHER RUDD; Fiscal Year: 2000

Detail Information

Publications248 found, 100 shown here

  1. pmc Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation
    Bijay S Jaiswal
    Department of Molecular Biology, Genentech Inc, South San Francisco, CA 94080, USA
    Cancer Cell 16:463-74. 2009
    ..Oncogenic activating mutations in the p110alpha catalytic subunit of the heterodimeric p110/p85 PI3K enzyme are frequent in human cancers...
  2. ncbi Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit
    Nabil Miled
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Science 317:239-42. 2007
    ..interface but in a polar surface patch that is a plausible docking site for other domains in the holo p110/p85 complex...
  3. doi NKX2-1/TITF1/TTF-1-Induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma
    Tomoya Yamaguchi
    Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Showa Ku, Nagoya 466 8550, Japan
    Cancer Cell 21:348-61. 2012
    ..Our findings thus identify ROR1 as an "Achilles' heel" in lung adenocarcinoma, warranting future development of therapeutic strategies for this devastating cancer...
  4. ncbi Phosphatidylinositol 3-kinase in interleukin 1 signaling. Physical interaction with the interleukin 1 receptor and requirement in NFkappaB and AP-1 activation
    S A Reddy
    Department of Biochemistry and Molecular Biology, Box 117, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 272:29167-73. 1997
    ..3-kinase (PI 3-kinase) activity but also induces the physical interaction of its type I receptor with the p85 regulatory subunit of PI 3-kinase...
  5. pmc Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase
    T Simoncini
    Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 407:538-41. 2000
    ..Our findings define a physiologically important non-nuclear oestrogen-signalling pathway involving the direct interaction of ER alpha with PI(3)K...
  6. pmc HIV-1 Tat promotes Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6-induced angiogenesis and tumorigenesis by regulating PI3K/PTEN/AKT/GSK-3β signaling pathway
    Feng Zhou
    State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People s Republic of China
    PLoS ONE 8:e53145. 2013
    ..Together, these results provide the first evidence that Tat might contribute to KS pathogenesis by synergizing with vIL-6, and identify PI3K/AKT pathway as a potential therapeutic target in AIDS-related KS patients...
  7. doi Association between phosphatidylinositol 3-kinase regulatory subunit p85alpha Met326Ile genetic polymorphism and colon cancer risk
    Li Li
    Department of Family Medicine Research Division, Case Western Reserve University, Cleveland, OH 44106 7136, USA
    Clin Cancer Res 14:633-7. 2008
    ..The phosphatidylinositol 3-kinase signaling pathway is frequently activated in cancer. Emerging evidence supports the p85alpha regulatory subunit gene, PIK3R1, as a novel oncogene...
  8. pmc Hypoxia up-regulates CD36 expression and function via hypoxia-inducible factor-1- and phosphatidylinositol 3-kinase-dependent mechanisms
    Bupe R Mwaikambo
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 284:26695-707. 2009
    ..Together, our findings indicate a novel mechanism by which hypoxia induces CD36 expression via activation of HIF-1 and the phosphatidylinositol 3-kinase pathway...
  9. pmc PIK3R1 (p85α) is somatically mutated at high frequency in primary endometrial cancer
    Mary E Urick
    Cancer Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 71:4061-7. 2011
    ..The goal of this study was to determine whether PIK3R1, which encodes p85α, the inhibitory subunit of PI3K, is mutated in endometrial carcinoma...
  10. pmc PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells
    G Castoria
    Dipartimento di Patologia Generale, Facolta di Medicina e Chirurgia, II Universita di Napoli, Via L De Crecchio, 7, 80138 Napoli, Italy
    EMBO J 20:6050-9. 2001
    The p85-associated phosphatidylinositol (PI) 3-kinase/Akt pathway mediates the oestradiol-induced S-phase entry and cyclin D1 promoter activity in MCF-7 cells...
  11. ncbi HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes
    I W Park
    Division of Experimental Medicine and Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA
    Blood 97:352-8. 2001
    ..These data indicate that the HIV-1 Tat protein may act as a protocytokine by causing the release of MCP-1 from the endothelial monolayer, and thereby facilitating monocyte transmigration into tissues via a PKC signaling pathway...
  12. pmc The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex
    Ji Luo
    Department of Systems Biology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    J Cell Biol 170:455-64. 2005
    ..The p85 regulatory subunit of PI 3-kinase is required to mediate the insulin-dependent recruitment of PI 3-kinase to the ..
  13. pmc Synergistic cooperation between methamphetamine and HIV-1 gsp120 through the P13K/Akt pathway induces IL-6 but not IL-8 expression in astrocytes
    Ankit Shah
    Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri Kansas City, Kansas City, Missouri, USA
    PLoS ONE 7:e52060. 2012
    ..This study therefore provides novel information regarding the interaction between MA and gp120 in terms of the expression of IL-6 and the mechanisms underlying potential synergy between MA and gp120 in astrocytes...
  14. pmc HIV-1 Nef in macrophage-mediated disease pathogenesis
    Susanna L Lamers
    BioInfoExperts, Thibodaux, LA, USA
    Int Rev Immunol 31:432-50. 2012
    ..Moreover, genetic variation in Nef may also guide the macrophage response. Herein, we review findings relating to the Nef-macrophage interaction and how this relationship contributes to disease pathogenesis...
  15. pmc Novel PI3K/Akt inhibitors screened by the cytoprotective function of human immunodeficiency virus type 1 Tat
    Yuri Kim
    Department of Pharmacy, Kyung Hee University, Seoul, South Korea
    PLoS ONE 6:e21781. 2011
    ..Compound K inhibited Akt phosphorylation. This study supports that Tat-expressing CHME5 cells are an effective model system for screening novel PI3K/Akt inhibitors...
  16. ncbi Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules
    S Rocchi
    INSERM U145, Nice, France
    Mol Endocrinol 12:914-23. 1998
    ..These include the regulatory subunit p85 of phosphatidylinositol 3-kinase and phosphotyrosine phosphatase, SHP-2...
  17. pmc Human immunodeficiency virus type 1 Tat accelerates Kaposi sarcoma-associated herpesvirus Kaposin A-mediated tumorigenesis of transformed fibroblasts in vitro as well as in nude and immunocompetent mice
    Xiuying Chen
    Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, PR China
    Neoplasia 11:1272-84. 2009
    ....
  18. ncbi Interaction of the Flt-1 tyrosine kinase receptor with the p85 subunit of phosphatidylinositol 3-kinase. Mapping of a novel site involved in binding
    S A Cunningham
    Department of Pharmacology, Texas Biotechnology Corporation, Houston 77030, USA
    J Biol Chem 270:20254-7. 1995
    We have examined the interactions of the p85 regulatory subunit of phosphatidylinositol 3-kinase with the endothelium-specific Flt-1 receptor tyrosine kinase using the yeast two-hybrid system...
  19. ncbi Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes
    R T Nolte
    Howard Hughes Medical Institute and Laboratory of Molecular Medicine, Children s Hospital, Boston, Massachusetts 02115, USA
    Nat Struct Biol 3:364-74. 1996
    ..The structures suggest a mechanism for the biological specificity exhibited by PI 3-kinase in its interactions with phosphoprotein partners...
  20. ncbi Tyrosine residue 719 of the c-kit receptor is essential for binding of the P85 subunit of phosphatidylinositol (PI) 3-kinase and for c-kit-associated PI 3-kinase activity in COS-1 cells
    H Serve
    Molecular Biology Program, Sloan Kettering Institute, New York, New York
    J Biol Chem 269:6026-30. 1994
    ..of the immediate events after binding of the kit ligand to the receptor is its association with the 85-kDa subunit (p85) of the phosphatidylinositol (PI) 3-kinase and the activation of the enzyme...
  21. pmc High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability
    Lydia W T Cheung
    Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054 1942
    Cancer Discov 1:170-85. 2011
    ..PIK3R1 (p85α) mutations occur at a higher rate in endometrial cancer than in any other tumor lineage, and PIK3R2 (p85β), not ..
  22. ncbi Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras
    P Rodriguez-Viciana
    Imperial Cancer Research Fund, London, United Kingdom
    Cell 89:457-67. 1997
    ..The ability of activated Ras to stimulate PI 3-kinase in addition to Raf is therefore important in Ras transformation of mammalian cells and essential in Ras-induced cytoskeletal reorganization...
  23. pmc Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor
    M Holgado-Madruga
    Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, 233 South 10th Street, Bluemle Life Science Building 1002, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 94:12419-24. 1997
    ..Hence, Gab1 has a major role in connecting TrkA with PI 3-kinase activation and for the promotion of cell survival by NGF...
  24. ncbi Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells
    Patrick Laprise
    Canadian Institutes of Health Research Group on Functional Development and Physiopathology of the Digestive Tract, Département d Anatomie et Biologie Cellulaire, Faculte de Medecine, Universite de Sherbrooke, Quebec J1H 5N4, Canada
    J Biol Chem 279:10157-66. 2004
    ..in intestinal cells not only severely alters adherens junction integrity but also prevents the recruitment of p85/PI3K to E-cadherin-mediated cell-cell contact and inhibits sucrase-isomaltase gene expression...
  25. pmc Overexpression of 14-3-3ζ in cancer cells activates PI3K via binding the p85 regulatory subunit
    C L Neal
    Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 31:897-906. 2012
    ..Mechanistically, 14-3-3ζ bound to the p85 regulatory subunit of PI3K and increased PI3K translocation to the cell membrane...
  26. ncbi The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations
    Chuan Hsiang Huang
    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 318:1744-8. 2007
    ..codes for p110alpha, the catalytic subunit of a phosphatidylinositol 3-kinase, isoform alpha (PI3Kalpha, p110alpha/p85). Here, we report a 3...
  27. ncbi Purification and characterization of phosphoinositide 3-kinase from rat liver
    C L Carpenter
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111
    J Biol Chem 265:19704-11. 1990
    ..Substitution of Mn2+ for Mg2+ results in only approximately 10% of the Mg2(+)-dependent activity. Physiological calcium concentrations have no effect on the enzyme activity. Phosphoinositide 3-kinase has a broad pH optimum around 7...
  28. pmc The phosphoinositide 3-kinase regulatory subunit p85alpha can exert tumor suppressor properties through negative regulation of growth factor signaling
    Cullen M Taniguchi
    Joslin Diabetes Center and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cancer Res 70:5305-15. 2010
    Phosphoinositide 3-kinase (PI3K) plays a critical role in tumorigenesis, and the PI3K p85 regulatory subunit exerts both positive and negative effects on signaling...
  29. pmc PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy
    Christel Thauvin-Robinet
    Equipe d Accueil 4271, Génétique des Anomalies du Developpement, Universite de Bourgogne, F 21079 Dijon, France
    Am J Hum Genet 93:141-9. 2013
    ..1945C>T [p.Arg649Trp]) present in four families. PIK3R1 encodes the p85α, p55α, and p50α regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play ..
  30. pmc PIK3R1 underexpression is an independent prognostic marker in breast cancer
    Magdalena Cizkova
    Oncogenetic Laboratory, Institut Curie, Hospital René Huguenin, Saint Cloud, France
    BMC Cancer 13:545. 2013
    ..The present study focused on the prognostic roles of PIK3CA and PIK3R1 genes and additional PI3K pathway-associated genes in breast cancer...
  31. ncbi HIV-1 gp120-mediated apoptosis of T cells is regulated by the membrane tyrosine phosphatase CD45
    Appakkudal R Anand
    Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:12289-99. 2006
    ..These results suggest a novel CD45-mediated mechanism for the HIV envelope-induced apoptosis of T cells...
  32. ncbi Type 1 TNF receptor forms a complex with and uses Jak2 and c-Src to selectively engage signaling pathways that regulate transcription factor activity
    Roxana Pincheira
    Department of Surgery and Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA
    J Immunol 181:1288-98. 2008
    ..These observations show that TNFR1 associates with and uses nonreceptor tyrosine kinases to engage signaling pathways, activate transcription factors, and modulate gene expression in cells...
  33. ncbi Identification of major tyrosine phosphorylation sites in the human insulin receptor substrate Gab-1 by insulin receptor kinase in vitro
    S Lehr
    Klinik II und Poliklinik für Innere Medizin at the Centre of Molecular Medicine of Cologne, Universitat zu Koln, Cologne, Germany
    Biochemistry 39:10898-907. 2000
    ..Y447, Y472, and Y619 exhibiting features (NYVPM motif) of potential binding sites for the regulatory subunit (p85) of phosphatidylinositol (PI)-3 kinase...
  34. pmc Interleukin-18/WNT1-inducible signaling pathway protein-1 signaling mediates human saphenous vein smooth muscle cell proliferation
    Venkatapuram Seenu Reddy
    Cardiothoracic Surgery, University of Texas Health Science Center, San Antonio, Texas
    J Cell Physiol 226:3303-15. 2011
    ....
  35. pmc SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors
    C J McGlade
    Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Mol Cell Biol 12:991-7. 1992
    ..The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-..
  36. pmc HIV-1 Tat protein induces the production of IDO in human monocyte derived-dendritic cells through a direct mechanism: effect on T cells proliferation
    Rémi Planès
    INSERM, U1043, Toulouse, France CNRS, U5282, Toulouse, France Université Paul Sabatier, EA 3038, Toulouse, France
    PLoS ONE 8:e74551. 2013
    ..By inducing IDO, Tat protein may be considered, as a viral pathogenic factor, in the dysregulation of the DC functions during HIV-1 infection. ..
  37. ncbi Expression of a mutated form of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in a Hodgkin's lymphoma-derived cell line (CO)
    M Jucker
    Institut fur Medizinische Biochemie und Molekularbiologie, Abteilung für Zelluläre Signaltransduktion, Universitatsklinikum Hamburg Eppendorf, Universitat Hamburg, Martinistrasse 52, 20246 Hamburg, Germany
    Leukemia 16:894-901. 2002
    ..PI3-kinase is a heterodimer consisting of an 85 kDa adapter protein (p85) containing one SH3 domain and two SH2 domains and a 110 kDa catalytic subunit (p110)...
  38. pmc SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling
    Kishan Kumar Chudasama
    K G Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N 5020 Bergen, Norway
    Am J Hum Genet 93:150-7. 2013
    ..A central component in this pathway is the p85α regulatory subunit, encoded by PIK3R1...
  39. pmc A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signaling
    G A Rodrigues
    Department of Pharmacology and Skirball Institute, New York University Medical Center, New York, New York 10016, USA
    Mol Cell Biol 20:1448-59. 2000
    ..A mutant of Gab1 unable to bind the p85 subunit of PI-3 kinase is defective in potentiating EGFR signaling, confirming a role for PI-3 kinase as a ..
  40. pmc Mutations in PIK3R1 cause SHORT syndrome
    David A Dyment
    Department of Genetics, Children s Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada
    Am J Hum Genet 93:158-66. 2013
    ..Our findings show that PIK3R1 mutations are the major cause of SHORT syndrome and suggest that the molecular mechanism of disease might involve downregulation of the PI3K-AKT-mTOR pathway...
  41. ncbi Insulin-like growth factor-1 potentiates platelet activation via the IRS/PI3Kalpha pathway
    Ingeborg Hers
    Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, UK
    Blood 110:4243-52. 2007
    ..tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K)...
  42. pmc Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR
    Alexandros Tzatsos
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA
    J Biol Chem 284:22525-34. 2009
    ..Overall, these data provide new insights in the molecular mechanisms by which mTORC1 inhibits PI 3-kinase/Akt signaling at the level of IRS-1 and suggest that mTOR signaling toward Akt is scaffold-dependent...
  43. ncbi Human immunodeficiency virus type 1 tat-mediated cytotoxicity of human brain microvascular endothelial cells
    Naveed Ahmed Khan
    Division of Pediatric Infectious Diseases, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Neurovirol 9:584-93. 2003
    ..Further understanding and characterization of Tat-HBMEC interactions should help us understand HIV-1 neuropathogenesis and develop strategies to prevent HIV-1 encephalopathy...
  44. pmc The v-Src SH3 domain binds phosphatidylinositol 3'-kinase
    X Liu
    Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Mol Cell Biol 13:5225-32. 1993
    ..Furthermore, the v-Src SH3 domain bound in vitro to the amino-terminal region of the p85 alpha subunit of PI 3'-kinase...
  45. ncbi Tyrosine phosphorylation of p85 relieves its inhibitory activity on phosphatidylinositol 3-kinase
    B D Cuevas
    Division of Medicine, Department of Molecular Therapeutics, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 276:27455-61. 2001
    Under resting conditions, the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) serves to both stabilize and inactivate the p110 catalytic subunit...
  46. ncbi Human ltk receptor tyrosine kinase binds to PLC-gamma 1, PI3-K, GAP and Raf-1 in vivo
    H Kozutsumi
    Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan
    Oncogene 9:2991-8. 1994
    ..wild-type ltk protein was tyrosine-phosphorylated in vivo and associated with SH2 containing proteins, PLC-gamma 1, p85 subunit of PI3-K and GAP, in vivo...
  47. ncbi Catalytically active TYK2 is essential for interferon-beta-mediated phosphorylation of STAT3 and interferon-alpha receptor-1 (IFNAR-1) but not for activation of phosphoinositol 3-kinase
    M R Rani
    Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 274:32507-11. 1999
    ..KR930 cells, but evident in U1.wt cells. In U1A-derived cells, the p85/p110 phosphoinositol 3-kinase isoform was associated with IFNAR-1 but not STAT3, and the association was ligand-..
  48. pmc A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response
    Jonathon 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
    ..Thus, p85alphaalpha forms a previously unrecognized link between the PI3K pathway, which is central to insulin action, and the regulation of the cellular response to ER stress, a state that when unresolved leads to insulin resistance...
  49. pmc Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase
    Ryaz B Chagpar
    Department of Biochemistry, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
    Proc Natl Acad Sci U S A 107:5471-6. 2010
    ..We demonstrate that ectopically expressed FLAG-tagged p85 coimmunoprecipitates endogenous PTEN in an epidermal growth factor dependent manner...
  50. ncbi HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells
    Maria Chiara Deregibus
    Cattedra di Nefrologia, Dipartimento di Medicina Interna Università di Torino, Centro Ricerca Medicina Sperimentale CeRMS, Italy
    J Biol Chem 277:25195-202. 2002
    ....
  51. pmc Small molecule inhibition of HIV-1-induced MHC-I down-regulation identifies a temporally regulated switch in Nef action
    Jimmy D Dikeakos
    Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA
    Mol Biol Cell 21:3279-92. 2010
    ..Together, these studies resolve the seemingly controversial models that describe Nef-induced MHC-I down-regulation and provide new insights into the mechanism of Nef action...
  52. ncbi LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation
    W Zhang
    Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 5430, USA
    Cell 92:83-92. 1998
    ..36-38 kDa protein, previously characterized by its association with Grb2, phospholipase C-gamma1, and the p85 subunit of phosphoinositide 3-kinase...
  53. ncbi Hyperosmotic stress inhibits insulin receptor substrate-1 function by distinct mechanisms in 3T3-L1 adipocytes
    Philippe Gual
    INSERM U 568 and l Institut Fédératif de Recherches 50, Faculte de Medecine, Avenue de Valombrose, 06107 Nice Cedex 02, France
    J Biol Chem 278:26550-7. 2003
    ..On the other hand, prolonged osmotic stress alters IRS-1 function by inducing its degradation, which could contribute to the down-regulation of insulin action...
  54. pmc Structure of lipid kinase p110β/p85β elucidates an unusual SH2-domain-mediated inhibitory mechanism
    Xuxiao Zhang
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Mol Cell 41:567-78. 2011
    Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. The structure of a p110β/p85β complex identifies an inhibitory function for the C-terminal SH2 domain (cSH2) of the p85 regulatory subunit...
  55. ncbi Mechanism of constitutive phosphoinositide 3-kinase activation by oncogenic mutants of the p85 regulatory subunit
    S Chandra Shekar
    Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Biol Chem 280:27850-5. 2005
    b>p85/p110 phosphoinositide 3-kinases regulate multiple cell functions and are frequently mutated in human cancer. The p85 regulatory subunit stabilizes and inhibits the p110 catalytic subunit...
  56. pmc Activation of phosphatidylinositol 3-kinase in response to interleukin-1 leads to phosphorylation and activation of the NF-kappaB p65/RelA subunit
    N Sizemore
    Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Mol Cell Biol 19:4798-805. 1999
    ..We have found that IL-1 stimulates interaction of the IL-1 receptor accessory protein with the p85 regulatory subunit of PI3K, leading to the activation of the p110 catalytic subunit...
  57. ncbi Tyr(612) and Tyr(632) in human insulin receptor substrate-1 are important for full activation of insulin-stimulated phosphatidylinositol 3-kinase activity and translocation of GLUT4 in adipose cells
    D L Esposito
    Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Endocrinology 142:2833-40. 2001
    ..Overexpression of IRS1-Y612 or IRS1-Y632 caused intermediate effects. Thus, both Tyr(612) and Tyr(632) are important for IRS-1 to fully activate PI3K and mediate translocation of GLUT4 in response to insulin...
  58. ncbi HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway
    Anastassia D Blagoveshchenskaya
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Cell 111:853-66. 2002
    ..These data provide new insights into the cellular basis of HIV-1 immunoevasion...
  59. pmc Signaling mechanism of HIV-1 gp120 and virion-induced IL-1beta release in primary human macrophages
    Ricky Cheung
    Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Immunol 180:6675-84. 2008
    ..This study identifies a novel signaling mechanism for HIV-1-induced IL-1beta production by primary human macrophages that may be involved in the neuropathogenesis of HIV-associated dementia...
  60. ncbi HIV-1 gp120-induced TNF-{alpha} production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways
    ChuHee Lee
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Leukoc Biol 78:1016-23. 2005
    ..These gp120-triggered signaling pathways may be responsible for inappropriate production of proinflammatory cytokines by macrophages, which are believed to play a role in immunopathogenesis and in neurological sequelae of AIDS...
  61. pmc Disrupted RabGAP function of the p85 subunit of phosphatidylinositol 3-kinase results in cell transformation
    M Dean Chamberlain
    Cancer Research Unit, Health Research Division, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan S7N 4H4, Canada
    J Biol Chem 283:15861-8. 2008
    ..GTPase-activating protein activity toward Rab5 and Rab4, an activity severely reduced by a single point mutation (p85-R274A)...
  62. ncbi Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors
    K Nishida
    Division of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Osaka, Japan
    Blood 93:1809-16. 1999
    ..Overexpression of Gab2 enhanced the gp130 or Src-related kinases-mediated ERK2 activation as that of Gab1 did. These data indicate that Gab-family molecules act as adapters for transmitting various signals...
  63. ncbi HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication
    Alison L Greenway
    Macfarlane Burnet Institute for Medical Research and Public Health, Cnr Commercial and Punt Roads, Melbourne, Victoria 3004, Australia
    J Biosci 28:323-35. 2003
    ....
  64. pmc Abrogation of PIK3CA or PIK3R1 reduces proliferation, migration, and invasion in glioblastoma multiforme cells
    Genevieve L Weber
    Ludwig Collaborative Laboratory, Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Oncotarget 2:833-49. 2011
    ..We conclude that PIK3R1, like PIK3CA, is a potential therapeutic target in GBM and that it also influences tumor cell growth and motility...
  65. ncbi Functional association of platelet endothelial cell adhesion molecule-1 and phosphoinositide 3-kinase in human neutrophils
    F Pellegatta
    Laboratory of Cardiovascular Pathophysiology, Department of Cardiology, Scientific Institute San Raffaele, Instituto di Ricovero e Cura a Carattere Scientifico, I 20132 Milan, Italy
    J Biol Chem 273:27768-71. 1998
    ..In conclusion, PECAM-1/CD31 appears to be one of the molecules functionally coupled to PI3K, suggesting that this enzyme may represent a common pathway of integrin and adhesiveness regulation in leukocytes...
  66. ncbi Activation of phosphatidylinositol 3-kinase/Akt pathway by androgen through interaction of p85alpha, androgen receptor, and Src
    Mei Sun
    Departments of Pathology and Interdisciplinary Oncology, University of South Florida College of Medicine and H Lee Moffitt Cancer Center, Tampa, Florida 33612, USA
    J Biol Chem 278:42992-3000. 2003
    ....
  67. ncbi Growth hormone, interferon-gamma, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1
    L S Argetsinger
    Department of Physiology, University of Michigan Medical School, Ann Arbor 48109 0622, USA
    J Biol Chem 270:14685-92. 1995
    ....
  68. ncbi A Grb2-associated docking protein in EGF- and insulin-receptor signalling
    M Holgado-Madruga
    Department of Microbiology and Immunology, Jefferson Cancer Institute, Philadelphia, Pennsylvania 19107, USA
    Nature 379:560-4. 1996
    ..Over-expression of Gab1 enhances cell growth and results in transformation. We conclude that Gab1 is a new protein in EGF and insulin receptor signalling which could integrate signals from different systems...
  69. ncbi Extracellular human immunodeficiency virus type-1 Tat protein activates phosphatidylinositol 3-kinase in PC12 neuronal cells
    D Milani
    Institute of Human Anatomy, University of Ferrara, 44100 Ferrara, Italy
    J Biol Chem 271:22961-4. 1996
    ..treatment with recombinant HIV-1 Tat protein, a significant increase in the tyrosine phosphorylation levels of the p85 regulatory subunit of PI 3-kinase was noticed in 48 h serum-starved PC12 cells...
  70. pmc Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation
    J M Backer
    Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital, Boston, MA
    EMBO J 11:3469-79. 1992
    ..rapid tyrosine phosphorylation during insulin stimulation and forms a stable complex containing the 85 kDa subunit (p85) of the phosphatidylinositol (PtdIns) 3'-kinase, but p85 is not tyrosyl phosphorylated...
  71. ncbi Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor
    A Craparo
    Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA
    J Biol Chem 270:15639-43. 1995
    ..In this study we demonstrate that IRS-1, SHC, and the p85 subunit of phosphatidylinositol 3-kinase interact directly and specifically with the IGFIR...
  72. pmc Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit
    A Musacchio
    Laboratory of Molecular Medicine, Children s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 93:14373-8. 1996
    ..We describe here the crystal structure of the BH domain from the p85 subunit of phosphatidylinositol 3-kinase at 2.0 A resolution...
  73. ncbi Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells
    J G Sathish
    Department of Medicine, University of Wales College of Medicine, Cardiff, Wales, United Kingdom
    J Immunol 166:1763-70. 2001
    ..We propose that this mechanism may exert a constitutive negative regulatory role upon T cell signaling...
  74. ncbi HIV-1 Nef associated PAK and PI3-kinases stimulate Akt-independent Bad-phosphorylation to induce anti-apoptotic signals
    D Wolf
    Department of Dermatology Erlangen, University of Erlangen Nurnberg, Erlangen, Germany
    Nat Med 7:1217-24. 2001
    ..Nef anti-apoptotic effects are likely a crucial mechanism for viral replication in the host and thus in AIDS pathogenesis...
  75. ncbi NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex
    R A Pauptit
    AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, England
    Acta Crystallogr D Biol Crystallogr 57:1397-404. 2001
    ..Use of maximum-likelihood refinement proved critical to be able to refine the poor starting models. The challenges typical of the use of NMR trial models in molecular replacement are discussed...
  76. ncbi Small GTPases and tyrosine kinases coregulate a molecular switch in the phosphoinositide 3-kinase regulatory subunit
    Tung O Chan
    Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Cancer Cell 1:181-91. 2002
    Phosphoinositide 3-kinase (PI3K) type IA is a heterodimer of a catalytic subunit, p110, and a regulatory subunit, p85. Here we show that p85 contains a GTPase-responsive domain and an inhibitory domain, which together form a molecular ..
  77. doi Akt/Nox2/NF-κB signaling pathway is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation
    Hong Sheng Zhang
    Beijing University of Technology, District of Chaoyang, China
    Arch Biochem Biophys 505:266-72. 2011
    ....
  78. pmc Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha
    Minghao Sun
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 107:15547-52. 2010
    ..Studies with isoform-specific inhibitors of p110 suggest that expression of p85 mutants in fibroblasts leads exclusively to an activation of p110alpha, and p110alpha is the sole mediator of p85 ..
  79. ncbi The p85alpha subunit of phosphatidylinositol 3'-kinase binds to and stimulates the GTPase activity of Rab proteins
    M Dean Chamberlain
    Cancer Research Unit, Health Research Division, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan S7N 4H4, Canada
    J Biol Chem 279:48607-14. 2004
    ..Cells expressing BH domain mutants of p85 show a reduced rate of PDGFR degradation as compared with wild type p85 expressing cells...
  80. ncbi Interaction of the molecular weight 85K regulatory subunit of the phosphatidylinositol 3-kinase with the insulin receptor and the insulin-like growth factor-1 (IGF- I) receptor: comparative study using the yeast two-hybrid system
    S Tartare-Deckert
    INSERM, Nice Cedex 2, France
    Endocrinology 137:1019-24. 1996
    ..have proposed that the two receptors interact directly with the SH2 domains of the Mr 85K regulatory subunit (p85) of PI 3- kinase via phosphorylated Y1322THM and Y1316AHM sequences located in the carboxyl-terminal domain of the ..
  81. pmc Differential association of phosphatidylinositol 3-kinase, SHIP-1, and PTEN with forming phagosomes
    Lynn A Kamen
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109 0620, USA
    Mol Biol Cell 18:2463-72. 2007
    ..SHIP1-YFP and p85-YFP were recruited to forming phagosomes...
  82. ncbi HIV-1 Tat induces tyrosine phosphorylation of p125FAK and its association with phosphoinositide 3-kinase in PC12 cells
    D Milani
    Department of Morphology and Embriology, University of Ferrara, Italy
    AIDS 12:1275-84. 1998
    ..To evaluate the signal transduction potential of HIV-1 Tat in a neuronal cell model...
  83. ncbi Differential signaling by the epidermal growth factor-like growth factors neuregulin-1 and neuregulin-2
    C S Crovello
    Division of Signal Transduction, Beth Israel Deaconess Medical Center and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 273:26954-61. 1998
    ..Since both of these cell lines express only two of the known ErbB receptors, our results imply that EGF-like ligands might elicit differential signaling within the context of a single receptor heterodimer...
  84. ncbi Infection of human immunodeficiency virus and intracellular viral Tat protein exert a pro-survival effect in a human microglial cell line
    Pauline Chugh
    Department of Microbiology and Immunology, School of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 672, Rochester, NY 14742, USA
    J Mol Biol 366:67-81. 2007
    ..We propose that the expression of Tat may enable HIV-1 infected microglia to survive throughout the course of infection, leading to persistent HIV-1 production and infection in the central nervous system...
  85. ncbi HIV-1 Nef blocks transport of MHC class I molecules to the cell surface via a PI 3-kinase-dependent pathway
    S A Swann
    Departments of Medicine and Microbiology and Immunology, The University of Michigan, Ann Arbor, Michigan 48109, USA
    Virology 282:267-77. 2001
    ..We propose that Nef diverts MHC-1 proteins into a PI 3-kinase-dependent transport pathway that prevents expression on the cell surface...
  86. ncbi HIV-1 Nef plays an essential role in two independent processes in CD4 down-regulation: dissociation of the CD4-p56(lck) complex and targeting of CD4 to lysosomes
    Y H Kim
    Laboratory of Molecular Virology, Samsung Biomedical Research Institute, Seoul, Korea
    Virology 257:208-19. 1999
    ....
  87. ncbi Dual phosphorylation of phosphoinositide 3-kinase adaptor Grb2-associated binder 2 is responsible for superoxide formation synergistically stimulated by Fc gamma and formyl-methionyl-leucyl-phenylalanine receptors in differentiated THP-1 cells
    Haruka Momose
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan
    J Immunol 171:4227-34. 2003
    The class Ia phosphoinositide (PI) 3-kinase consisting of p110 catalytic and p85 regulatory subunits is activated by Tyr kinase-linked membrane receptors such as FcgammaRII through the association of p85 with the phosphorylated receptors ..
  88. ncbi The Gab1 protein is a docking site for multiple proteins involved in signaling by the B cell antigen receptor
    R J Ingham
    Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 273:30630-7. 1998
    ..Far Western analysis showed that the SH2 domains of Shc, SHP-2, and the p85 subunit of phosphatidylinositol 3-kinase could bind directly to tyrosine-phosphorylated Gab1 isolated from ..
  89. pmc Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation
    Alexandros Tzatsos
    Boston University School of Medicine, Massachusetts 02118, USA
    Mol Cell Biol 26:63-76. 2006
    ..Thus, diabetes-related hyperglycemia hyperactivates the mTOR pathway and may lead to insulin resistance due to suppression of IRS-1-dependent PI3-kinase/Akt signaling...
  90. pmc Phosphatidylinositol 3-kinase regulates human immunodeficiency virus type 1 replication following viral entry in primary CD4+ T lymphocytes and macrophages
    Fleur Francois
    Division of Infectious Diseases, Mt Sinai School of Medicine, 1 Gustave L Levy Place, New York, NY 10029, USA
    J Virol 77:2539-49. 2003
    ..This type of host-virus interaction has implications for anti-HIV therapeutics that target cellular signaling machinery...
  91. ncbi Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index
    T Hansen
    Steno Diabetes Center and Hagedorn Research Institute, Glostrup University Hospital, Copenhagen, Denmark
    Diabetes 46:494-501. 1997
    ..In itself, the gene variant does not confer an increased risk of diabetes...
  92. ncbi Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells
    P Borgatti
    Institute of Human Anatomy, University of Ferrara, Italy
    Eur J Immunol 27:2805-11. 1997
    ..Taken together, these data suggest that the anti-apoptotic activity of low concentrations of Tat protein on Jurkat cells is mediated by a PI 3-kinase/Akt pathway...
  93. ncbi TGF-beta 1 modulates EGF-stimulated phosphatidylinositol 3-kinase activity in human airway smooth muscle cells
    V P Krymskaya
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Am J Physiol 273:L1220-7. 1997
    ....
  94. pmc Characterization of the Met326Ile variant of phosphatidylinositol 3-kinase p85alpha
    Katrine Almind
    Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 99:2124-8. 2002
    ..Thus, the Met-326Ile variant of p85alpha is functional for intracellular signaling and adipocyte differentiation but has small alterations in protein expression and activity that could play a role in modifying insulin action...
  95. ncbi Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells
    T B van Dijk
    Institute of Hematology, Erasmus University Rotterdam, Rotterdam, The Netherlands
    Blood 96:3406-13. 2000
    ..These findings suggest that p62Dok-1 may function as an important scaffold molecule in cKit-mediated signaling...
  96. ncbi Peptidoglycan induces nuclear factor-kappaB activation and cyclooxygenase-2 expression via Ras, Raf-1, and ERK in RAW 264.7 macrophages
    Bing Chang Chen
    School of Respiratory Therapy, Taipei Medical University, 250 Wu Hsing Street, Taipei 110, Taiwan
    J Biol Chem 279:20889-97. 2004
    ..Our data demonstrate for the first time that PGN activates the Ras/Raf-1/ERK pathway, which in turn initiates IKKalpha/beta and NF-kappaB activation, and ultimately induces COX-2 expression in RAW 264.7 macrophages...
  97. ncbi A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family
    C Ponzetto
    Department of Biomedical Sciences and Oncology, University of Torino Medical School, Italy
    Cell 77:261-71. 1994
    ..The same bidentate motif is conserved in the evolutionarily related receptors Sea and Ron, suggesting that in all members of the HGF/SF receptor family, signal transduction is channeled through a multifunctional binding site...
  98. pmc ADP-ribosylation factor 1 controls the activation of the phosphatidylinositol 3-kinase pathway to regulate epidermal growth factor-dependent growth and migration of breast cancer cells
    Pierre Luc Boulay
    Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, Quebec H3C 3J7, Canada
    J Biol Chem 283:36425-34. 2008
    ..These results uncover a novel molecular mechanism by which ARF1 regulates breast cancer cell growth and invasion during cancer progression...
  99. ncbi Inhibition of tyrosine kinase activation blocks the down-regulation of CXC chemokine receptor 4 by HIV-1 gp120 in CD4+ T cells
    S B Su
    Laboratory of Molecular Immunoregulation, Division of Basic Sciences, SAIC Frederick National Cancer Institute, MD 21702, USA
    J Immunol 162:7128-32. 1999
    ..Thus, a CD4-associated signaling molecule(s) including p56lck is activated by gp120 and is required for the down-regulation of CXCR4...
  100. pmc Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain
    T A Gustafson
    Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA
    Mol Cell Biol 15:2500-8. 1995
    ..The SAIN domain appears to represent a novel motif which is able to interact with autophosphorylated receptors such as the IR...
  101. pmc 1-Phosphatidylinositol 3-kinase activity is required for insulin-stimulated glucose transport but not for RAS activation in CHO cells
    K Hara
    Second Department of Internal Medicine, Kobe University School of Medicine, Japan
    Proc Natl Acad Sci U S A 91:7415-9. 1994
    ..In this study, the stable overexpression in a Chinese hamster ovary (CHO) cell line of a mutant p85 alpha (delta p85) protein, which lacks a binding site for p110, disrupted the complex formation between IRS-1 and the ..

Research Grants62

  1. Regulation and Function of hVps34 in Insulin Signaling
    Jonathan M Backer; Fiscal Year: 2010
    ..While the function of p85/p110 PI 3-kinases in insulin responsive cells is well documented, the Class III PI 3-kinase, hVps34, also plays an ..
  2. Non-apoptotic functions of caspases
    STEVEN MILES FRISCH; Fiscal Year: 2012
    ..the calpain-mediated cleavage of guanine nucleotide exchange factors (GEFs) for Rac and/or by regulating the p85 subunit of PI3- Kinase...
  3. Role of PI 3-Kinase isoforms in insulin action
    C Ronald Kahn; Fiscal Year: 2013
    ..This includes differences in the activity and properties of the different regulatory (p85) and catalytic (p110) subunits of PI 3-kinase;important effects of stoichiometry between regulatory and catalytic ..
  4. ANG II AND IGF-1 INTERACTION IN CARDIOVASCULAR TISSUE
    James Sowers; Fiscal Year: 2003
    ..In order to interrupt the PI3-kinase pathway, they will transfect a dominant-negative p85 construct using adenovirus and FuGENE methodologies in VSMC and neonatal cardiomyocytes, respectively...
  5. Selective Insulin Resistance- Diabetic Cardiovascular Diseases
    George L King; Fiscal Year: 2013
    ..2) Identify the role of phospho-Thr86 of p85/PI3K in causing selective insulin resistance in EC and correlate the changes of phospho-Thr86/p85 with vascular ..
  6. p85/p110 PI3 Kinase-Structure, function and Physiology
    Jonathan M Backer; Fiscal Year: 2013
    ..The Class IA PI 3-kinase is a dimer containing distinct regulatory (p85) and catalytic (p110) subunits, both of which are frequently mutated in human cancer...
  7. P3K, RETROVIRAL ONCOGENE AND HOMOLOG OF PI 3-KINASE
    Peter K Vogt; Fiscal Year: 2013
    ..analysis will concentrate on the interactions between p110[unreadable] and Ras as well as p110[unreadable] and p85. These interactions are critical to the oncogenicity of p110[unreadable];they are fundamentally changed in the ..
  8. Myocardial ischemic activation of the Akt pathway
    STEPHEN ARMSTRONG; Fiscal Year: 2007
    ..bDG) assembles a complex of signaling molecules that allows an association with and activation of the p85 subunit of PI-3K, initiating Akt phosphorylation...
  9. Novel Function of PI 3-Kinase in Calcium Regulation
    Ching Shih Chen; Fiscal Year: 2004
    ..a molecular genetic approach in which Jurkat T cells are stably transfected with a dominant-negative form of the p85 regulatory subunit to suppress the activity of endogenous PI 3-kinase...
  10. CD4/CD8 P56LCK AND ASSOCIATED KINASES
    CHRISTOPHER RUDD; Fiscal Year: 2000
    ..We propose to define whether there is preferential recruitment of the p85 (alpha,beta) and p110 (alpha,beta) subunits, whether PI 3-kinase binding regulates lck activity and to define the ..
  11. Role of Integrins/ECM in Controlling IGF-I Actions
    David Robert Clemmons; Fiscal Year: 2013
    ..We will deter- mine the role of SHP-2 transfer to p85 in regulating the activation of Rac-1 and Cdc-42. The necessity of SHP...
  12. Akt-regulated pathways in platelet function
    Donna S Woulfe; Fiscal Year: 2011
    ..Our preliminary studies show that arrestins form agonist-dependent complexes with p85-PI3K subunits in human platelets...
  13. Determinants of Efficacy to the Akt Inhibitor Perifosine in Colorectal Cancer
    Cathy Eng; Fiscal Year: 2012
    ..Endpoint: Pharma- codynamic biomarker changes will correlate with efficacy of perifosine therapy. ..
  14. PI3K Signaling in Juvenile Myelomonocytic Leukemia
    CHARLES B GOODWIN; Fiscal Year: 2013
    ..of both PI3K regulatory subunits p851 and p852, with activating PTPN11 mutants to explore the hypothesis that both p85 subunits contribute to gain-of-function mutant Shp2-mediated GM-CSF hypersensitivity...
  15. SECOND MESSENGERS IN THE RETINA
    RAJU VS RAJALA; Fiscal Year: 2012
    ..Interestingly, conditional deletion of p85[unreadable], which regulates class IA PI3K, from cones resulted in an age-related cone degeneration...
  16. RGS: A Molecular Switch Regulating Irreversible ASM Growth/Contraction in Asthma
    REYNOLD ALEXANDER PANETTIERI; Fiscal Year: 2012
    ..of regulators of G-protein signaling (RGS) proteins which inactivate G proteins and co-localize with phospho-p85 (p-p85) PI3K to facilitate S6K1 activation...
  17. Combinatorial Approach for Reducing Invasive Potential of Melanoma Cells
    Farrukh Afaq; Fiscal Year: 2013
    ..found that fisetin treatment reduced melanoma cell invasion by inhibiting the protein expression of PI3K (p110a and p85) and phosphorylation of AKT at Ser473 and Thr308...
  18. Prevention of Acute Lung Injury by IL-6 activated STAT3
    Ana Moran; Fiscal Year: 2010
    ....
  19. ADIPOCYTE PROTEIN SECRETION AND INSULIN ACTION
    Harvey Lodish; Fiscal Year: 2007
    ..Overexpression of wild type proteins will be assessed for p85 and p110 subunits of PI3-kinase, Akt, PKCepsilon, PKCzeta, PIP kinase, dynamin l and 2, caveolins 1, 2, and 3, and ..
  20. The role of BRD7 in the regulation of endoplasmic reticulum and glucose homeostas
    Sang Won Park; Fiscal Year: 2013
    ..in obesity condition and that its interaction with the regulatory subunits of phosphatidyl-inositol3-kinase (PI3K), p85[unreadable] and p85[unreadable], is crucial for its function...
  21. ER Stress, Insulin Signaling and Metabolism
    Umut Ozcan; Fiscal Year: 2011
    ..Our recent findings implicate p85αand p85β, the regulatory subunits of Phosphatidyl Inositol 3-Kinase (PI3K), as obligatory ..
  22. JAK2 signaling in erythropoiesis
    LILY JUNSHEN HUANG; Fiscal Year: 2013
    ..This process involves a new function of the p85 subunit of PI3K and is PI3K kinase activity-independent...
  23. The Role of PI3K in Growth Regulation
    Lewis C Cantley; Fiscal Year: 2013
    ..The second aim is to evaluate the role of the p85 subunit of Class 1a PI3Ks in BRD7 function...
  24. Molecular mechanisms of PI3K activation in non-small cell lung cancer
    Jeffrey A Engelman; Fiscal Year: 2010
    ..PI3K consists of a dimer between the regulatory subunit, p85, and the catalytic subunit, p110...
  25. Mechanisms of Receptor Regulated Na+-H+ Exchange
    Diane L Barber; Fiscal Year: 2013
    ..on how phosphoinositide 3-kinase is pH sensitive, based on our recent structural and biochemical findings that its p85 regulatory subunit is a pH sensor...
  26. Polypeptide modification for enhanced brain delivery
    Alexander V Kabanov; Fiscal Year: 2013
    ..The previous work produced a conjugate of leptin with Pluronic P85 that is centrally active, has a long half-life in blood, is enzymatically resistant, crosses the BBB by a non-..
  27. The Bcl-2-p85/PI3K signaling axis
    Xiao Kun Zhang; Fiscal Year: 2013
    ..Our objectives are to use integrated multidisciplinary approaches to address several issues regarding the Bcl-2/p85 interaction: 1)...
  28. A Novel Regulator of Pl-3-Kinase in Human Liver Cancer
    Marie C DeFrances; Fiscal Year: 2010
    ..PI3K is composed of a p85 regulatory subunit and a p110 catalytic subunit...
  29. TGF BETA RECEPTORS AND CELL PROLIFERATION
    Edward B Leof; Fiscal Year: 2013
    ..scaffolding function in profibrotic TGF-? signaling whereby it couples the ligand-activated type I TGF-?R to the p85 subunit of PI3K, the most upstream component regulating non-Smad pathways such as PAK2/c-Abl and Akt/mTOR;and (ii) ..
  30. NUTRITIONAL AND BIOCHEMICAL/GENETIC MARKERS OF CANCER
    Jing Ma; Fiscal Year: 2007
    ..following proteins: the GH1, insulin receptor substrate (IRS)-1, IRS-2, posphatidylinositol 3'- kinase (PI3K)-p85 subunit, peroxisome proliferator-activated receptor (PPARgamma, a nuclear hormone receptor that plays a key role in ..
  31. A TEMPERATURE-SENSITIVE RETROVIRUS SPLICING MUTANT
    Ralph Arlinghaus; Fiscal Year: 1991
    ..5 kb viral mRNA which is translated to produce the transforming protein termed P85/gag- mos. This splicing reaction occurs readily at 28 degrees C in cells but not at 39 degrees C...
  32. PHOSPHOINOSITIDE-3 KINASE IN CARDIAC HYPERTROPHY
    Peter Kang; Fiscal Year: 2004
    ..Two known downstream targets of PI3K are the Akt (protein kinase B) and the p70/p85 ribosomal S6 kinase (S6K). However, their role in the cardiac growth in vivo has not been established...
  33. GTP BINDING PROTEINS AND INSULIN RECEPTOR SINGNALING
    CHIN SUNG; Fiscal Year: 1999
    ..stimulation of rat HTC hepatoma and other cells one or more signaling complexes form that consists of: the IR; the p85 subunit of phosphatidylinositol-3-kinase; Ras GTPase activating protein (GAP); and p62 GAP-associated protein...
  34. SHP2 and SIRP modulate erbB signals in astrocytes
    DONALD O ROURKE; Fiscal Year: 2005
    ..SHP2 also associates with the p85 regulatory subunit of P13-K in cells in which P13-K pathway activation is unimpaired...
  35. Mechanisms of Growth Factor-Estrogen Receptor Crosstalk
    Stephen Safe; Fiscal Year: 2006
    ..will also determine the biological significance of direct ERalpha interactions with Src-SH2, G proteins, the p85 regulatory subunit of PI3-K and the IGF-1 receptor...
  36. IRS-PROTEIN AND TYPE 1 INTERFERON SIGNALING
    Leonidas Platanias; Fiscal Year: 2000
    ..The best characterized member of this family, IRS-1, binds the SH2 domains of the p85 regulatory subunit of the phosphatidylinositol 3'-kinase in an IFNalpha-dependent manner, and such an association ..
  37. SIGNAL TRANSDUCTION BY THE ECK RECEPTOR TYROSINE KINASE
    Claudius Vincenz; Fiscal Year: 1999
    ..The first was the p85 subunit of PI3-kinase...
  38. SIGNAL TRANSDUCTION BY THE C-MET RECEPTOR
    Lloyd Cantley; Fiscal Year: 1999
    ..events initiated by the novel second messenger PIP3 (Specific Aim 1a), and 3) elucidating the role of the p85 and p110 subunits of the PI 3-K in morphogenesis using a series of deletional mutants of the enzyme (Specific Aim ..
  39. P13K IN RADIATION RESISTANCE OF HUMAN MELANOMA CELLS
    ZE EV RONAI; Fiscal Year: 2000
    ..melanoma cells which show reduced resistance to a radiation dominant negative mutant of regulatory subunit p85 or catalytic subunit P110 of P13K...
  40. ENDOCYTIC REGULATION OF HEPATOCYTE GROWTH
    MARK MC NIVEN; Fiscal Year: 1999
    ..we have cloned and sequenced genes from rat liver encoding a novel dynamin (dynamin2) and a dynamin- like protein (p85-DLP)...
  41. IRS2 AND B CELL HOMEOSTASIS
    Achsah Keegan; Fiscal Year: 2000
    ..This phosphorylated IRS -2 molecule co-precipitates with the p85 subunit of PI-3 kinase in both resting and activated B-cells...
  42. DESIGN AND SYNTHESIS OF POLY L PROLINE II PEPTIDE MIMICS
    JOSE MADALENGOITIA; Fiscal Year: 2002
    ..1) erbB2/erbB3 transphosphorylation; 2) erbB2/erbB3 association with the Scr homology 2 (SH2) domains of the p85 subunit of the phosphotidylinositol 3 kinase (P13K), and 3) association of the P13K Src homology 3 (SH3) domain ..
  43. Analysis of Bidirectional Signaling Mechanisms for BTLA and HVEm
    MICHELLE SANDAU; Fiscal Year: 2010
    ..Also, a conserved Grb2 site can recruit PI3K P85, which may allow for pro- survival signals. Therefore, BTLA has both positive and negative signaling potential...
  44. PI KINASES, CANALICULAR TRANSPORTERS AND CHOLESTASIS
    IRWIN ARIAS; Fiscal Year: 2003
    ..fluorescence microscopic techniques and novel reagents and experimental models, including genetically engineered p85-/- PI 3- kinase mice, the specific trafficking of canalicular transporters and the role of PI 3-kinase and its ..
  45. Influence of P-glycoprotein in treating brain tumors
    Donald Miller; Fiscal Year: 2006
    ..in the brain under normal conditions and following P-gp modulation with either polymer formulation, Pluronic P85, or the small molecule P-gp inhibitor, GF918120...
  46. ERYTHROCYTE PROTEIN ANTIGENS REGULATED BY IN-LU
    Marilyn Telen; Fiscal Year: 1993
    ..In addition, a second protein (p85), bearing Lutheran antigens, will also be purified...
  47. MECHANISMS OF T LYMPHOCYTE DEVELOPMENT
    Barton Haynes; Fiscal Year: 2000
    ..transgenic mice, constructed CD7 homologous recombinant (gene knockout) mice, and demonstrated association of the p85 subunit of PI-3 kinase with the cytoplasmic domain of CD7 after ligation of the CD7 extracellular domain in Jurkat ..
  48. The Role of CbL in AbL Signaling and Leukemia
    Hua Gu; Fiscal Year: 2006
    ..phosphorylated by c-Abl and associate with c-Abl and other signaling molecules downstream of c-Abl, such as CrkL, p85 of PI-3 kinase and Vav, upon c-Abl activation...
  49. Signaling mechanisms in oligodendrocytes
    Robin Miskimins; Fiscal Year: 2006
    ..The proposed experiments focus on the rote of the regulatory subunit of PI3 kinase, p85, in expression of the MBP gene. p85 greatly enhances MBP promoter activity...
  50. DNA POLYMERASES
    Stuart Linn; Fiscal Year: 1999
    ..antibodies to p260, the other "core" subunit, p55, and also to peptides which were shown to complex pol epsilon (p85, p70, p49) were obtained...
  51. TYROSINE PHOSPHATASES IN ENDOTHELIAL GROWTH CONTROL
    Takamune Takahashi; Fiscal Year: 2009
    ..associates with FGF receptor, and 7) CD148 cytoplasmic domain interacts with- and dephosphorylates the PI3 kinase p85 subunit and p120 catenin molecules...
  52. Estrogen and Mechanisms of Cardiomyocyte Protection
    Richard Karas; Fiscal Year: 2009
    ..cardiomyocytes, E2 induces the formation of a signaling complex that contains Estrogen Receptor a, cSrc-kinase, the p85 regulatory subunit of PI3 kinase, and Striatin, a membrane-associated scaffold protein...
  53. DOWNSTREAM ELEMENTS IN IRS 1 SIGNALING--P55PIK
    Morris White; Fiscal Year: 2000
    ..The p55/PIK is a newly discovered SH2-protein which shares characteristics with p85, a principle regulatory element linking phosphatidylinositol-3 kinase to IRS-1 and other growth factor receptors...
  54. Indentification of AKT2/aPKC Substrates in Adipocytes
    Prem Sharma; Fiscal Year: 2005
    ..pathways such as knockout of the IR, IRS-2 or AKT2, can produce diabetes, whereas, knockout of the p85 subunit of PI3K, AKT1, IRS-1 or GLUT4 does not...
  55. REGULATION OF LUNG ENDOTHELIAL CONTRACTION/PERMEABILITY
    JOE GARCIA; Fiscal Year: 2002
    ..Specific Aim #1 will examine the interaction between p60src kinase, the p85 kD actin-binding protein, cortactin, and EC MLCK in the context of endothelial cell cytoskeletal rearrangement...
  56. Hypothalamic Leptin and Insulin Signaling
    Jennifer Hill; Fiscal Year: 2006
    ..pattern of PI3K within the hypothalamus using double-labeled I3HH and IHC for NPY, POMC, and the PI3K subunits p85 and p110...
  57. COSTIMULATION OF T LYMPHOCYTES OF CD28
    John Imboden; Fiscal Year: 2003
    ..Also, a 50 kD protein that binds CD28 at Tyr 170 and is closely related to phosphatidylinositol 3'-kinase p85 will be characterized...
  58. MECHANISMS OF PROTEIN ACCUMULATION IN RENAL HYPERTROPHY
    Harold Franch; Fiscal Year: 2002
    ..It should also lay the ground work for further investigations into the mechanisms behind renal hypertrophy. ..
  59. Is Tissue ACE Required for Diabetic Renal Damage?
    Harold Franch; Fiscal Year: 2005
    ..We believe that this approach will not only critically test our hypothesis, but will also lay the ground work for future studies into the role of ACE in the diabetic kidney. ..
  60. Sensory Gating in Schizophrenia: Multiple Measures
    Julie Patterson; Fiscal Year: 2004
    ....
  61. Potent inhibitors of Anthrax Lethal Factor
    Peter Vogt; Fiscal Year: 2003
    ..Libraries will be targeted using the structural information available for LF, supplemented by information from point mutations of the substrate. Information from our previous synthesis of metalloprotease inhibitors will also be used. ..
  62. Graphical models for linkage disequilibrium in genetic mapping
    Alun Thomas; Fiscal Year: 2010
    ..For this aim of the project we intend to apply the methods developed to dense genotype assays obtained for distantly related breast cancer cases in extended Utah pedigrees. ..