Cloning and characterization of hdlg: the human homologue of the Drosophila discs large tumor suppressor binds to protein 4.1.
The Drosophila discs large tumor suppressor protein, dlg, has been shown to regulate the growth of imaginal discs during embryogenesis [Woods, D. F. & Bryant, P. J. (1991) Cell 66, 451-464]. We cloned and sequenced the complete cDNA for a human B-lymphocyte 100-kDa protein that shares 60% amino acid identity with dlg. This human homologue of Drosophila discs large (hdlg) contains a C-terminal domain homologous to the known guanylate kinases, a src homology 3 region motif, and three dlg homology repeats. Two nonhomologous domains that can contain in-frame insertions result in at least four alternatively spliced isoforms of hdlg. Several hdlg RNA transcripts are widely distributed in human and murine tissues, and the protein is localized to regions of cell-cell contact. Protein 4.1, the defining member of a family that includes talin and merlin/schwannomin, has the same cellular localization as hdlg, and two sites within hdlg associate in vitro with the 30-kDa N-terminal domain of protein 4.1.
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Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138.
Marfatia
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Branton
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Chishti
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular / Q000379:methods; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D016147:Genes, Tumor Suppressor; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D007301:Insect Hormones / Q000096:biosynthesis* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009479:Neuropeptides; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins
D003598:Cytoskeletal Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D007301:Insect Hormones; D008565:Membrane Proteins; D009479:Neuropeptides; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; C070350:dlg1 protein, Drosophila