Phosphorylation-dependent binding of 14-3-3 to the polarity protein Par3 regulates cell polarity in mammalian epithelia

Toby W Hurd, Shuling Fan, Chia Jen Liu, Hye Kyong Kweon, Kristina Hakansson, Ben Margolis

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2082-90
Number of pages9
JournalCurrent biology : CB
Volume13
Issue number23
Publication statusPublished - 2 Dec 2003

Keywords

  • 14-3-3 Proteins
  • Animals
  • Blotting, Western
  • Carrier Proteins
  • Cell Polarity
  • Cells, Cultured
  • Epithelium
  • Gene Expression
  • Immunohistochemistry
  • Mammals
  • Phosphorylation
  • Precipitin Tests
  • Tight Junctions
  • Tyrosine 3-Monooxygenase

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