Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • October 19, 2006

Research

keywords

  • Cell Cycle Proteins
  • Epithelial Cells
  • ErbB Receptors
  • Membrane Proteins
  • Protein Processing, Post-Translational
  • Signal Transduction
  • Tight Junctions

Identity

PubMed Central ID

  • PMC1630420

Scopus Document Identifier

  • 33750489040

Digital Object Identifier (DOI)

  • 10.1038/sj.emboj.7601384

PubMed ID

  • 17053785

Additional Document Info

volume

  • 25

issue

  • 21