The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42.
PAR (partitioning-defective) proteins, which were first identified in the nematode Caenorhabditis elegans, are essential for asymmetric cell division and polarized growth, whereas Cdc42 mediates establishment of cell polarity. Here we describe an unexpected link between these two systems. We have identified a family of mammalian Par6 proteins that are similar to the C. elegans PDZ-domain protein PAR-6. Par6 forms a complex with Cdc42-GTP, with a human homologue of the multi-PDZ protein PAR-3 and with the regulatory domains of atypical protein kinase C (PKC) proteins. This assembly is implicated in the formation of normal tight junctions at epithelial cell-cell contacts. Thus, Par6 is a key adaptor that links Cdc42 and atypical PKCs to Par3.
Joberty
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Markey Center for Cell Signaling, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908-0577, USA. gmj4h@virginia.edu
Petersen
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Gao
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Macara
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D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006160:Guanosine Triphosphate / Q000378:metabolism; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016415:Sequence Alignment; D013379:Substrate Specificity; D019108:Tight Junctions / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D062826:Zonula Occludens-1 Protein; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D007527:Isoenzymes; D046911:Macromolecular Substances; D008565:Membrane Proteins; C518597:Par6 protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; C512642:par-6 protein, C elegans; D006160:Guanosine Triphosphate; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C; C503256:RHOQ protein, human; C503260:Rhoq protein, mouse; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins