• Login
    View Item 
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of eScholarship@UMassChanCommunitiesPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywordsThis CollectionPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywords

    My Account

    LoginRegister

    Help

    AboutSubmission GuidelinesData Deposit PolicySearchingAccessibilityTerms of UseWebsite Migration FAQ

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    A novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytes

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Zhou, Qiong L.
    Jiang, Zhen Y.
    Mabardy, Allan S.
    Del Campo, Claudia M.
    Lambright, David G.
    Holik, John
    Fogarty, Kevin E.
    Straubhaar, Juerg R.
    Nicoloro, Sarah M.
    Chawla, Anil
    Czech, Michael P.
    Show allShow less
    UMass Chan Affiliations
    Program in Molecular Medicine
    Department of Physiology
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2010-09-03
    Keywords
    3T3-L1 Cells
    Adipocytes
    Animals
    Blood Proteins
    Enzyme Activation
    Gene Expression Regulation
    Gene Silencing
    Glucose
    Glucose Transporter Type 4
    Humans
    Insulin
    Intracellular Signaling Peptides and
    Proteins
    Mice
    Phosphatidylinositol Phosphates
    Phosphoproteins
    Phosphorylation
    Protein Structure, Tertiary
    Protein Transport
    Proto-Oncogene Proteins c-akt
    Ribosomal Protein S6 Kinases, 70-kDa
    Sequence Homology, Amino Acid
    Life Sciences
    Medicine and Health Sciences
    Women's Studies
    Show allShow less
    
    Metadata
    Show full item record
    Link to Full Text
    http://www.jbc.org/content/285/36/27581.full.pdf+html
    Abstract
    Protein kinase B/Akt protein kinases control an array of diverse functions, including cell growth, survival, proliferation, and metabolism. We report here the identification of pleckstrin homology-like domain family B member 1 (PHLDB1) as an insulin-responsive protein that enhances Akt activation. PHLDB1 contains a pleckstrin homology domain, which we show binds phosphatidylinositol PI(3,4)P(2), PI(3,5)P(2), and PI(3,4,5)P(3), as well as a Forkhead-associated domain and coiled coil regions. PHLDB1 expression is increased during adipocyte differentiation, and it is abundant in many mouse tissues. Both endogenous and HA- or GFP-tagged PHLDB1 displayed a cytoplasmic disposition in unstimulated cultured adipocytes but translocated to the plasma membrane in response to insulin. Depletion of PHLDB1 by siRNA inhibited insulin stimulation of Akt phosphorylation but not tyrosine phosphorylation of IRS-1. RNAi-based silencing of PHLDB1 in cultured adipocytes also attenuated insulin-stimulated deoxyglucose transport and Myc-GLUT4-EGFP translocation to the plasma membrane, whereas knockdown of the PHLDB1 isoform PHLDB2 failed to attenuate insulin-stimulated deoxyglucose transport. Furthermore, adenovirus-mediated expression of PHLDB1 in adipocytes enhanced insulin-stimulated Akt and p70 S6 kinase phosphorylation, as well as GLUT4 translocation. These results indicate that PHLDB1 is a novel modulator of Akt protein kinase activation by insulin.
    Source
    J Biol Chem. 2010 Sep 3;285(36):27581-9. Epub 2010 Jun 28. Link to article on publisher's site
    DOI
    10.1074/jbc.M110.146886
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/51000
    PubMed ID
    20587420
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1074/jbc.M110.146886
    Scopus Count
    Collections
    UMass Chan Faculty and Researcher Publications

    entitlement

     

    Related items

    Showing items related by title, author, creator and subject.

    • Thumbnail

      Dynamic Regulation at the Neuronal Plasma Membrane: Novel Endocytic Mechanisms Control Anesthetic-Activated Potassium Channels and Amphetamine-Sensitive Dopamine Transporters: A Dissertation

      Gabriel, Luke R. (2013-06-13)
      Endocytic trafficking dynamically regulates neuronal plasma membrane protein presentation and activity, and plays a central role in excitability and plasticity. Over the course of my dissertation research I investigated endocytic mechanisms regulating two neuronal membrane proteins: the anesthetic-activated potassium leak channel, KCNK3, as well as the psychostimulant-sensitive dopamine transporter (DAT). My results indicate that KCNK3 internalizes in response to Protein Kinase C (PKC) activation, using a novel pathway that requires the phosphoserine binding protein, 14-3-3β, and demonstrates for the first time regulated KCNK3 channel trafficking in neurons. Additionally, PKC-mediated KCNK3 trafficking requires a non-canonical endocytic motif, which is shared exclusively between KCNK3 and sodium-dependent neurotransmitter transporters, such as DAT. DAT trafficking studies in intact ex vivo adult striatal slices indicate that DAT endocytic trafficking has both dynamin-dependent and –independent components. Moreover, DAT segregates into two populations at the neuronal plasma membrane: trafficking-competent and -incompetent. Taken together, these results demonstrate that novel, non-classical endocytic mechanisms dynamically control the plasma membrane presentation of these two important neuronal proteins.
    • Thumbnail

      Selective interaction of JNK protein kinase isoforms with transcription factors

      Gupta, Shashi; Barrett, Tamera; Whitmarsh, Alan J.; Cavanagh, Julie; Sluss, Hayla Karen; Derijard, Benoit; Davis, Roger J. (1996-06-03)
      The JNK protein kinase is a member of the MAP kinase group that is activated in response to dual phosphorylation on threonine and tyrosine. Ten JNK isoforms were identified in human brain by molecular cloning. These protein kinases correspond to alternatively spliced isoforms derived from the JNK1, JNK2 and JNK3 genes. The protein kinase activity of these JNK isoforms was measured using the transcription factors ATF2, Elk-1 and members of the Jun family as substrates. Treatment of cells with interleukin-1 (IL-1) caused activation of the JNK isoforms. This activation was blocked by expression of the MAP kinase phosphatase MKP-1. Comparison of the binding activity of the JNK isoforms demonstrated that the JNK proteins differ in their interaction with ATF2, Elk-1 and Jun transcription factors. Individual members of the JNK group may therefore selectively target specific transcription factors in vivo.
    • Thumbnail

      Role of the Raf/mitogen-activated protein kinase pathway in p21ras desensitization

      Klarlund, Jes K.; Cherniack, Andrew D.; McMahon, Martin; Czech, Michael P. (1996-07-12)
      Desensitization of p21(ras) after stimulation of cells by growth factors and phorbol 12-myristate 13-acetate (PMA) correlates with hyperphosphorylation of the guanine nucleotide exchange factor Son-of-sevenless (Sos) and its dissociation from the adaptor protein Grb2 (Cherniack, A., Klarlund, J. K., Conway, B. R., and Czech, M. P. (1995) J. Biol. Chem. 270, 1485-1488). To test the role of the Raf/mitogen-activated protein (MAP) kinase pathway, we utilized cells expressing a chimera composed of the catalytic domain of p74Raf-1 and the hormone binding domain of the estradiol receptor (DeltaRaf-1:ER). Estradiol markedly stimulated DeltaRaf-1:ER and the downstream MEK and MAP kinases in these cells as well as Sos phosphorylation. However, the dissociation of Grb2 from Sos observed in response to PMA was not apparent upon DeltaRaf-1:ER activation. Furthermore, stimulation of DeltaRaf-1:ER did not impair GTP loading of p21(ras) in response to platelet-derived growth factor or epidermal growth factor. We conclude that activation of the Raf/MAP kinase pathway alone in these cells is insufficient to cause disassembly of Sos from Grb2 or to interrupt the ability of Sos to catalyze activation of p21(ras).
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Lamar Soutter Library, UMass Chan Medical School | 55 Lake Avenue North | Worcester, MA 01655 USA
    Quick Guide | escholarship@umassmed.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.