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Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2

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  • Yi-Ping Hsueh

    (Howard Hughes Medical Institute and Department of Neurobiology Massachusetts General Hospital and Harvard Medical School)

  • Ting-Fang Wang

    (Howard Hughes Medical Institute and Department of Neurobiology Massachusetts General Hospital and Harvard Medical School
    Harvard University)

  • Fu-Chia Yang
  • Morgan Sheng

    (Howard Hughes Medical Institute and Department of Neurobiology Massachusetts General Hospital and Harvard Medical School)

Abstract

Membrane-associated guanylate kinases (MAGUKs) contain multiple protein-binding domains that allow them to assemble specific multiprotein complexes in particular regions of the cell1,2. CASK/LIN-2, a MAGUK required for EGF receptor localization and signalling in Caenorhabditis elegans, contains a calmodulin-dependent protein kinase-like domain followed by PDZ, SH3 and guanylate kinase-like domains3,4,5. In adult rat brain, CASK is concentrated at neuronal synapses and binds to the cell-surface proteins neurexin and syndecan6,7,8 and the cytoplasmic proteins Mint/LIN-10 and Veli/LIN-7 (refs 4, 9, 10). Here we report that, through its guanylate kinase domain, CASK interacts with Tbr-1, a T-box transcription factor that is involved in forebrain development11,12. CASK enters the nucleus and binds to a specific DNA sequence (the T-element) in a complex with Tbr-1. CASK acts as a coactivator of Tbr-1 to induce transcription of T-element containing genes, including reelin, a gene that is essential for cerebrocortical development. Our findings show that a MAGUK which is usually associated with cell junctions has a transcription regulation function.

Suggested Citation

  • Yi-Ping Hsueh & Ting-Fang Wang & Fu-Chia Yang & Morgan Sheng, 2000. "Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2," Nature, Nature, vol. 404(6775), pages 298-302, March.
    • Handle: RePEc:nat:nature:v:404:y:2000:i:6775:d:10.1038_35005118
    DOI: 10.1038/35005118
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    Cited by:

    1. Manvendra Singh & Ying Zhao & Vinicius Daguano Gastaldi & Sonja M. Wojcik & Yasmina Curto & Riki Kawaguchi & Ricardo M. Merino & Laura Fernandez Garcia-Agudo & Holger Taschenberger & Nils Brose & Dani, 2023. "Erythropoietin re-wires cognition-associated transcriptional networks," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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