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MafA stability in pancreatic beta cells is regulated by glucose and is dependent on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 3.

MafA stability in pancreatic beta cells is regulated by glucose and is dependent on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 3. Research Abstract Details 

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  • MafA stability in pancreatic beta cells is regulated by glucose and is dependent on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 3. Abstract Text:

    song-iee hanSong-Iee Han,shinsaku aramataShinsaku Aramata,kunio yasudaKunio Yasuda,kohsuke kataokaKohsuke Kataoka,song-iee hanSong-Iee Han,shinsaku aramataShinsaku Aramata,kunio yasudaKunio Yasuda,kohsuke kataokaKohsuke Kataoka,

    Regulation of insulin gene expression by glucose in pancreatic beta cells is largely dependent on a cis-regulatory element, termed RIPE3b/C1, in the insulin gene promoter. MafA, a member of the Maf family of basic leucine zipper (bZip) proteins, is a beta-cell-specific transcriptional activator that binds to the C1 element. Based on increased C1-binding activity, MafA protein levels appear to be up-regulated in response to glucose, but the underlying molecular mechanism for this is not well understood. In this study, we show evidence supporting that the amino-terminal region of MafA is phosphorylated at multiple sites by glycogen synthase kinase 3 (GSK3) in beta cells. Mutational analysis of MafA and pharmacological inhibition of GSK3 in MIN6 beta cells strongly suggest that the rate of MafA protein degradation is regulated by glucose, that MafA is constitutively phosphorylated by GSK3, and that phosphorylation is a prerequisite for rapid degradation of MafA under low-glucose conditions. Our data suggest a new glucose-sensing signaling pathway in islet beta cells that regulates insulin gene expression through the regulation of MafA protein stability.

    MafA stability in pancreatic beta cells is regulated by glucose and is dependent on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 3. Publishing Authors By Initials

    si hanSI Han,s aramataS Aramata,k yasudaK Yasuda,k kataokaK Kataoka,si hanSI Han,s aramataS Aramata,k yasudaK Yasuda,k kataokaK Kataoka,

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    MafA stability in pancreatic beta cells is regulated by glucose and is dependent on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 3. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Molecular and cellular biology

    VOLUME: 27

    Page Numbers: 6593-605

    Journal Abbreviation: Mol. Cell. Biol.

    ISSN: 0270-7306

    DAY: 6

    MONTH: 08

    YEAR: 2007

    MafA stability in pancreatic beta cells is regulated by glucose and is dependent on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 3. Information

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    LANGUAGE: eng

    NlmUniqueID: 8109087

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    Grant and Affiliation Information for MafA stability in pancreatic beta cells is regulated by glucose and is dependent on its constitutive phosphorylation at multiple sites by glycogen synthase kinase 3.

    AFFILIATION: Laboratory of Molecular and Developmental Biology, Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma, Japan.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Mol Cell Biol

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