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dc.contributor.authorZhou, Qiong L.
dc.contributor.authorJiang, Zhen Y.
dc.contributor.authorMabardy, Allan S.
dc.contributor.authorDel Campo, Claudia M.
dc.contributor.authorLambright, David G.
dc.contributor.authorHolik, John
dc.contributor.authorFogarty, Kevin E.
dc.contributor.authorStraubhaar, Juerg R.
dc.contributor.authorNicoloro, Sarah M.
dc.contributor.authorChawla, Anil
dc.contributor.authorCzech, Michael P.
dc.date2022-08-11T08:11:05.000
dc.date.accessioned2022-08-23T17:32:40Z
dc.date.available2022-08-23T17:32:40Z
dc.date.issued2010-09-03
dc.date.submitted2012-06-22
dc.identifier.citationJ Biol Chem. 2010 Sep 3;285(36):27581-9. Epub 2010 Jun 28. <a href="http://dx.doi.org/10.1074/jbc.M110.146886">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Linking)
dc.identifier.doi10.1074/jbc.M110.146886
dc.identifier.pmid20587420
dc.identifier.urihttp://hdl.handle.net/20.500.14038/51000
dc.description.abstractProtein 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=20587420&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.jbc.org/content/285/36/27581.full.pdf+html
dc.subject3T3-L1 Cells
dc.subjectAdipocytes
dc.subjectAnimals
dc.subjectBlood Proteins
dc.subjectEnzyme Activation
dc.subjectGene Expression Regulation
dc.subjectGene Silencing
dc.subjectGlucose
dc.subjectGlucose Transporter Type 4
dc.subjectHumans
dc.subjectInsulin
dc.subjectIntracellular Signaling Peptides and
dc.subjectProteins
dc.subjectMice
dc.subjectPhosphatidylinositol Phosphates
dc.subjectPhosphoproteins
dc.subjectPhosphorylation
dc.subjectProtein Structure, Tertiary
dc.subjectProtein Transport
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectRibosomal Protein S6 Kinases, 70-kDa
dc.subjectSequence Homology, Amino Acid
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectWomen's Studies
dc.titleA novel pleckstrin homology domain-containing protein enhances insulin-stimulated Akt phosphorylation and GLUT4 translocation in adipocytes
dc.typeArticle
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume285
dc.source.issue36
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/wfc_pp/536
dc.identifier.contextkey3017593
html.description.abstract<p>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.</p>
dc.identifier.submissionpathwfc_pp/536
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentDepartment of Physiology
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages27581-9


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