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 language | English |
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Pages (from-to) | 2082-90 |
Number of pages | 9 |
Journal | Current biology : CB |
Volume | 13 |
Issue number | 23 |
Publication status | Published - 2 Dec 2003 |
Keywords / Materials (for Non-textual outputs)
- 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