Article: article from journal or magazin.
Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells.
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
14-3-3 Proteins, Animals, Binding Sites/genetics, Body Patterning/genetics, Carrier Proteins/antagonists & inhibitors, Carrier Proteins/genetics, Cell Differentiation/genetics, Cell Membrane/genetics, Cell Membrane/metabolism, Cell Polarity/physiology, Drosophila Proteins/genetics, Drosophila Proteins/metabolism, Drosophila melanogaster/embryology, Drosophila melanogaster/genetics, Epithelial Cells/cytology, Epithelial Cells/metabolism, Intracellular Signaling Peptides and Proteins, Membrane Proteins/genetics, Membrane Proteins/metabolism, Oocytes/cytology, Oocytes/growth & development, Phosphorylation, Protein Binding/genetics, Protein Kinase C/genetics, Protein Kinase C/metabolism, Protein Kinases/genetics, Protein Kinases/metabolism, Protein-Serine-Threonine Kinases, Tyrosine 3-Monooxygenase/genetics, Tyrosine 3-Monooxygenase/metabolism
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