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  • The EMBO Journal (2006) 25, 5058 - 5070
  • doi:10.1038/sj.emboj.7601384

Published online: 19 October 2006

Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling

Yiguo Wang1,2, Dan Du1,2, Longhou Fang1,2, Guang Yang1,2, Chenyi Zhang1, Rong Zeng1, Axel Ullrich3, Friedrich Lottspeich4 and Zhengjun Chen1,5

  1. Key Laboratory of Proteomics and Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
  2. Graduate School of the Chinese Academy of Sciences, Beijing, China
  3. Department of Molecular Biology, Max-Planck-Institute of Biochemistry, Martinsried, Germany
  4. Protein Analytik, Max-Planck-Institute of Biochemistry, Martinsried, Germany
  5. SHARF Laboratory, Shanghai, China

Correspondence to:

Zhengjun Chen, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China. Tel.: 86 21 54921081; Fax: 86 21 54921081; E-mail: zjchen@sibs.ac.cn

Received 5 May 2006; Accepted 12 September 2006

The conserved polarity complex, comprising the partitioning-defective (Par) proteins Par3 and Par6, and the atypical protein kinase C, functions in various cell-polarization events and asymmetric cell divisions. However, little is known about whether and how external stimuli-induced signals may regulate Par3 function in epithelial cell polarity. Here, we found that Par3 was tyrosine phosphorylated through phosphoproteomic profiling of pervanadate-induced phosphotyrosine proteins. We also demonstrated that the tyrosine phosphorylation event induced by multiple growth factors including epidermal growth factor (EGF) was dependent on activation of Src family kinase (SFK) members c-Src and c-Yes. The tyrosine residue 1127 (Y1127) of Par3 was identified as the major EGF-induced phosphorylation site. Moreover, we found that Y1127 phosphorylation reduced the association of Par3 with LIM kinase 2 (LIMK2), thus enabling LIMK2 to regulate cofilin phosphorylation dynamics. Substitution of Y1127 for phenylalanine impaired the EGF-induced Par3 and LIMK2 dissociation and delayed epithelial tight junction (TJ) assembly considerably. Collectively, these data suggest a novel, phosphotyrosine-dependent fine-tuning mechanism of Par3 in epithelial TJ assembly controlled by the EGF receptor-SFK signaling pathway.

  • Keywords:

    • EGFR signaling,
    • LIMK2,
    • Par3,
    • phosphotyrosine,
    • tight junction