title: MAGI-1, a membrane-associated guanylate kinase with a unique arrangement of protein-protein interaction domains.
abstract: Membrane-associated guanylate kinase (MAGUK) proteins participate in the assembly of multiprotein complexes on the inner surface of the plasma membrane at regions of cell-cell contact. MAGUKs are characterized by three types of protein-protein interaction modules: the PDZ domain, the Src homology 3 (SH3) domain, and the guanylate kinase (GuK) domain. The arrangement of these domains is conserved in all previously known MAGUKs: either one or three PDZ domains in the NH2-terminal half, followed by the SH3 domain, followed by a COOH-terminal GuK domain. In this report, we describe the cDNA cloning and subcellular distribution of MAGI-1, a MAGUK with three unique structural features: 1) the GuK domain is at the NH2 terminus, 2) the SH3 domain is replaced by two WW domains, and 3) it contains five PDZ domains. MAGI-1 mRNA was detected in several adult mouse tissues. Sequence analysis of overlapping cDNAs revealed the existence of three splice variants that are predicted to encode MAGI-1 proteins with different COOH termini. The longest variant, MAGI-1c, contains three bipartite nuclear localization signals in its unique COOH-terminal sequence and was found predominantly in the nucleus of Madin-Darby canine kidney cells. A shorter form lacking these signals was found primarily in membrane and cytoplasmic fractions. This distribution, which is reminiscent of that seen for the tight junction protein ZO-1, suggests that MAGI-1 may participate in the transmission of regulatory signals from the cell surface to the nucleus.
authors.affiliation: Department of Biochemistry, The University of Texas Health Science Center, San Antonio, Texas 78284-7760, USA.
authors.forename: I
authors.initials: I
authors.lastname: Dobrosotskaya
authors.forename: R K
authors.initials: RK
authors.lastname: Guy
authors.forename: G L
authors.initials: GL
authors.lastname: James
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000737:chemistry; D004285:Dogs; D051528:Guanylate Kinases; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D014018:Tissue Distribution; D018909:src Homology Domains
chemical_list: D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C033652:postsynaptic density proteins; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases