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

doi:10.1074/jbc.M506933200

Back

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

Journal article

Open access

Peer reviewed

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

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

The Journal of biological chemistry, Vol.281(3), pp.1725-1730

01/20/2006

DOI: 10.1074/jbc.M506933200

PMID: 16293617

Files and links (1)

url

https://doi.org/10.1074/jbc.M506933200View

Published (Version of record) Open Access

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.

Immunohistochemistry

Phosphorylation

Respiratory Mucosa - cytology

Humans

Phosphoprotein Phosphatases - metabolism

Respiratory Mucosa - physiology

Kinetics

Tissue Donors

Protein Phosphatase 2

Receptor, Epidermal Growth Factor - physiology

Details

Title: Subtitle: erbB1 functions as a sensor of airway epithelial integrity by regulation of protein phosphatase 2A activity
Creators: Paola D Vermeer - Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA
Lacey Panko
Michael J Welsh
Joseph Zabner
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.281(3), pp.1725-1730
DOI: 10.1074/jbc.M506933200
PMID: 16293617
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: K01 DK60113-01 / NIDDK NIH HHS R01 HL075276-01A1 / NHLBI NIH HHS
Language: English
Date published: 01/20/2006
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
Record Identifier: 9984017217602771

Metrics

20 Record Views

12 Times Cited - Web of Science