erbB1 functions as a sensor of airway epithelial integrity by regulation of protein phosphatase 2A activity

Paola D. Vermeer, Lacey Panko, Michael J. Welsh, Joseph Zabner

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Two enzymes, protein phosphatase 2A and atypical protein kinase C, are associated with the tight junction and regulate its function. For example, phosphorylation of the tight junction protein occludin is required for its incorporation into the junction. The association of a kinase and phosphatase with the tight junction suggests that a balance between their activities exists and is required for normal tight junction function. This hypothesis predicts that loss of epithelial integrity may disrupt this balance in such a way as to facilitate restoration of epithelial integrity. Our previous data have shown that apically localized growth factors segregate from their basolaterally localized erbB receptors. Loss of epithelial integrity allows ligand access to the basolateral membrane where it immediately binds to and activates erbB receptors. We found that activation of erbB1 leads to phosphorylation of protein phosphatase 2A, inhibiting its activity. Importantly, this phosphorylation event was dependent on factors in the overlying airway surface liquid; washing away this liquid prevented phosphorylation. erbB1-mediated inhibition of phosphatase activity would shift the balance in favor of the kinase such that tight junction proteins would regain their phosphorylation, allowing for their incorporation into the junction complex. This mechanism provides a rapid means of sensing the loss of epithelial integrity and subsequently restoring barrier function.

Original languageEnglish (US)
Pages (from-to)1725-1730
Number of pages6
JournalJournal of Biological Chemistry
Volume281
Issue number3
DOIs
StatePublished - Jan 20 2006

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Protein Phosphatase 2
Phosphorylation
Tight Junctions
Sensors
Tight Junction Proteins
Phosphoric Monoester Hydrolases
Phosphotransferases
Occludin
Regain
Liquids
Washing
Restoration
Intercellular Signaling Peptides and Proteins
Chemical activation
Association reactions
Ligands
Membranes
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

erbB1 functions as a sensor of airway epithelial integrity by regulation of protein phosphatase 2A activity. / Vermeer, Paola D.; Panko, Lacey; Welsh, Michael J.; Zabner, Joseph.

In: Journal of Biological Chemistry, Vol. 281, No. 3, 20.01.2006, p. 1725-1730.

Research output: Contribution to journalArticle

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