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

Membrane-associated guanylate kinases (MAGUKs) contain multiple protein-binding domains that allow them to assemble specific multiprotein complexes in particular regions of the cell. 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 domains. In ...
adult rat brain, CASK is concentrated at neuronal synapses and binds to the cell-surface proteins neurexin and syndecan and the cytoplasmic proteins Mint/LIN-10 and Veli/LIN-7. Here we report that, through its guanylate kinase domain, CASK interacts with Tbr-1, a T-box transcription factor that is involved in forebrain development. 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.
Mesh Terms:
Animals, Binding Sites, Biological Transport, COS Cells, Caenorhabditis elegans, Calcium-Calmodulin-Dependent Protein Kinases, Cell Adhesion Molecules, Neuronal, Cell Nucleus, Cells, Cultured, Cerebral Cortex, DNA, DNA-Binding Proteins, Extracellular Matrix Proteins, Gene Expression Regulation, Genes, Reporter, Guanylate Kinase, Helminth Proteins, Hippocampus, Membrane Proteins, Mice, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Nucleoside-Phosphate Kinase, Protein Binding, Rats, Regulatory Sequences, Nucleic Acid, Serine Endopeptidases, Transcription Factors, Transcription, Genetic
Nature
Date: Mar. 16, 2000
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