title: Phosphorylation-dependent binding of 14-3-3 to the polarity protein Par3 regulates cell polarity in mammalian epithelia.
abstract: The mammalian homologs of the C. elegans partitioning-defective (Par) proteins have been demonstrated to be necessary for establishment of cell polarity. In mammalian epithelia, the Par3/Par6/aPKC polarity complex is localized to the tight junction and regulates its formation and positioning with respect to basolateral and apical membrane domains. Here we demonstrate a previously undescribed phosphorylation-dependent interaction between a mammalian homolog of the C. elegans polarity protein Par5, 14-3-3, and the tight junction-associated protein Par3. We identify phosphorylated serine 144 as a site of 14-3-3 binding. Expression of a Par3 mutant that contains serine 144 mutated to alanine (S144A) results in defects in epithelial cell polarity. In addition, overexpression of 14-3-3zeta results in a severe disruption of polarity, whereas overexpression of a 14-3-3 mutant that is defective in binding to phosphoproteins has no effect on cell polarity. Together, these data suggest a novel, phosphorylation-dependent mechanism that regulates the function of the Par3/Par6/aPKC polarity complex through 14-3-3 binding.
authors.affiliation: Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Toby W
authors.initials: TW
authors.lastname: Hurd
authors.forename: Shuling
authors.initials: S
authors.lastname: Fan
authors.forename: Chia Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Hye Kyong
authors.initials: HK
authors.lastname: Kweon
authors.forename: Kristina
authors.initials: K
authors.lastname: Hakansson
authors.forename: Ben
authors.initials: B
authors.lastname: Margolis
mesh_terms: D048948:14-3-3 Proteins; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D004848:Epithelium / Q000502:physiology; D015870:Gene Expression; D007150:Immunohistochemistry; D008322:Mammals; D009419:Nerve Tissue Proteins; D010766:Phosphorylation; D011233:Precipitin Tests; D019108:Tight Junctions / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; D014446:Tyrosine 3-Monooxygenase