The Drosophila discs large (dlg) tumor suppressor gene was first identified in Drosophila through genetic analysis of germline mutations. Several mammalian homologs were subsequently identified and categorized into a protein family termed MAGUK (membrane-associated guanylate kinase homolog). Human homologs of dlg include hdlg-1 (rat SAP 97) and NE-dlg (neuronal and endocrine dlg). The rat synaptic protein PSD-95 (also designated SAP 90) also shares homology with these proteins. MAGUKs are localized at the membrane-cytoskeleton interface and contain several distinct domains which suggest a role for these proteins in intracellular signal transduction. Interaction of hdlg-1 and NE-dlg with the tumor suppresor protein APC suggest that MAGUK proteins may also play a role in regulation of growth.
