title: Drosophila 14-3-3/PAR-5 is an essential mediator of PAR-1 function in axis formation.
abstract: PAR-1 kinases are required to determine the anterior-posterior (A-P) axis in C. elegans and Drosophila, but little is known about their molecular function. We identified 14-3-3 proteins as Drosophila PAR-1 interactors and show that PAR-1 binds a domain of 14-3-3 distinct from the phosphoserine binding pocket. PAR-1 kinases phosphorylate proteins to generate 14-3-3 binding sites and may therefore directly deliver 14-3-3 to these targets. 14-3-3 mutants display identical phenotypes to par-1 mutants in oocyte determination and the polarization of the A-P axis. Together, these results indicate that PAR-1's function is mediated by the binding of 14-3-3 to its substrates. The C. elegans 14-3-3 protein, PAR-5, is also required for A-P polarization, suggesting that this is a conserved mechanism by which PAR-1 establishes cellular asymmetries.
authors.affiliation: The Wellcome Trust/Cancer Research UK Institute and Department of Genetics, University of Cambridge, CB2 1QR, Cambridge, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Benton
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Palacios
authors.forename: Daniel
authors.initials: D
authors.lastname: St Johnston
mesh_terms: D048948:14-3-3 Proteins; D000818:Animals; D001368:Axis, Cervical Vertebra / Q000502:physiology; D001665:Binding Sites; D029742:Caenorhabditis elegans Proteins; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005260:Female; D005854:Germ Cells; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; C106207:par-5 protein, C elegans; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases