CLONING AND CHARACTERIZATION OF HDLG - THE HUMAN HOMOLOG OF THE DROSOPHILA DISKS LARGE TUMOR-SUPPRESSOR BINDS TO PROTEIN-4.1

The Drosophila discs large tumor suppressor protein, dlg, has been sho wn to regulate the growth of imaginal discs during embryogenesis [Wood s, D. F. & Bryant, P. J. (1991) Cell 66, 451-464]. We cloned and seque nced the complete cDNA for a human B-lymphocyte 100-kDa protein that s hares 60% amino acid identity with dlg. This human homologue of Drosop hila discs large (hdlg) contains a C-terminal domain homologous to the known guanylate kinases, a src homology 3 region moth, and three dlg homology repeats. Two nonhomologous domains that can contain in-frame insertions result in at least four alternatively spliced isoforms of h dlg. Several hdlg RNA transcripts are widely distributed in human and murine tissues, and the protein is localized to regions of cell-cell c ontact. Protein 4.1, the defining member of a family that includes tal in and merlin/schwannomin, has the same cellular localization as hdlg, and two sites within hdlg associate in vitro with the 30-kDa N-termin al domain of protein 4.1.