Abstract
PAR-1 kinases are required for polarity in diverse cell types, such as epithelial cells, where they localize laterally. PAR-1 activity is believed to be transduced by binding of 14-3-3 proteins to its phosphorylated substrates, but the relevant targets are unknown. We show that PAR-1 phosphorylates Bazooka/PAR-3 on two conserved serines to generate 14-3-3 binding sites. This inhibits formation of the Bazooka/PAR-6/aPKC complex by blocking Bazooka oligomerization and binding to aPKC. In epithelia, this complex localizes apically and defines the apical membrane, whereas Bazooka lacking PAR-1 phosphorylation/14-3-3 binding sites forms ectopic lateral complexes. Lateral exclusion by PAR-1/14-3-3 cooperates with apical anchoring by Crumbs/Stardust to restrict Bazooka localization, and loss of both pathways disrupts epithelial polarity. PAR-1 also excludes Bazooka from the posterior of the oocyte, and disruption of this regulation causes anterior-posterior polarity defects. Thus, antagonism of Bazooka by PAR-1/14-3-3 may represent a general mechanism for establishing complementary cortical domains in polarized cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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14-3-3 Proteins
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Animals
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Binding Sites / genetics
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Body Patterning / genetics
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Differentiation / genetics
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Cell Membrane / genetics
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Cell Membrane / metabolism
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Cell Polarity / physiology*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / embryology*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism
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Epithelial Cells / cytology
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Epithelial Cells / metabolism*
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Glycogen Synthase Kinase 3
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Intracellular Signaling Peptides and Proteins*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Oocytes / cytology
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Oocytes / growth & development
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Oocytes / metabolism
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Phosphorylation
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Protein Binding / genetics
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Protein Kinase C / genetics
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Protein Kinase C / metabolism
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Protein-Serine-Threonine Kinases
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Tyrosine 3-Monooxygenase / genetics
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Tyrosine 3-Monooxygenase / metabolism*
Substances
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14-3-3 Proteins
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Carrier Proteins
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Drosophila Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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baz protein, Drosophila
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crb protein, Drosophila
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Tyrosine 3-Monooxygenase
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Protein Kinases
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Protein-Serine-Threonine Kinases
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PKC-3 protein
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Protein Kinase C
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Glycogen Synthase Kinase 3
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Par-1 protein, Drosophila