title: Multiple splice variants of Par3 and of a novel related gene, Par3L, produce proteins with different binding properties.
abstract: The partitioning-defective 3 (par3) gene encodes a protein with three postsynaptic density90/DiscslargeA/ZO-1 (PDZ) domains that is required for cell polarity establishment in metazoans. Par3 is a component of a protein complex that can include Cdc42-GTP, Par6 and atypical protein kinase Cs (aPKCs). We now describe the identification of a related human gene, Par3L. Both Par3L and Par3 are expressed as numerous alternatively spliced variants. Although Par3 expression appears to be ubiquitous, that of Par3L is more restricted. Multiple variants are often expressed simultaneously within a specific cell type or tissue. Although all of the Par3L/Par3 isoforms can associate with tight junctions in epithelial cells, they show different binding properties. No Par3L isoforms and only a subset of Par3 isoforms detectably bind aPKCs. These data suggest that aPKC binding or phosphorylation is not required for targeting of Par3/Par3L to cell-cell contacts. Par3L isoforms also show differential binding to Par6. Despite these differences, the N-terminal region of Par3L, like that of Par3, can disrupt the formation of tight junctions when ectopically expressed in Madin-Darby canine kidney (MDCK) cells.
authors.affiliation: Center for Cell Signaling and Department of Pharmacology, University of Virginia Health Science Center, P.O. Box 800577, Charlottesville, VA 22908-0577, USA. ig2q@virginia.edu
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.forename: Ian G
authors.initials: IG
authors.lastname: Macara
authors.forename: Gérard
authors.initials: G
authors.lastname: Joberty
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D018938:Caco-2 Cells; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D015870:Gene Expression; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D019108:Tight Junctions / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; C509689:PARD3 protein, human; C471157:PARD3B protein, human; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D011493:Protein Kinase C