MAGI-1, a membrane-associated guanylate kinase with a unique arrangement of protein-protein interaction domains

Irina Dobrosotskaya, Rodney K. Guy, Guy L. James

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

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.

Original languageEnglish
Pages (from-to)31589-31597
Number of pages9
JournalJournal of Biological Chemistry
Volume272
Issue number50
DOIs
StatePublished - Dec 12 1997

Bibliographical note

Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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