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This Article Full Text Full Text (PDF) All Versions of this Article: 91/1/131    most recent expphysiol.2005.031823v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Treharne, K. J Articles by Mehta, A Search for Related Content PubMed PubMed Citation Articles by Treharne, K. J Articles by Mehta, A Related Collections Symposia Papers

¹ Division of Maternal and Child Health Sciences, University of Dundee, Dundee DD1 9SY, UK

Abstract

A considerable body of evidence indicates that the intracellular chloride concentration ([Cl^–]_i) is an important regulatory signal in epithelial ion transport. [Cl^–]_i regulates the open channel probability of sodium and chloride channels, the rate of chloride channel recycling to the apical membrane, cell volume homeostasis, the activity of sodium-coupled chloride entry pathways and G-protein activity. Cell volume goes awry in epithelial cells bearing mutant forms of the cystic fibrosis (CF) transmembrane conductance regulator protein (CFTR); however, the pathways that mediate this [Cl^–]_i effect at the apical membrane of polarized epithelia are unknown. Recently, we proposed a mechanism for the transduction of in vitro chloride concentration into a phosphorylation signal to proteins within the apical membrane of respiratory epithelia. Our studies show that an apically enriched plasma membrane fraction from a variety of species, including sheep, human and mouse airway, contains at least two membrane-bound protein kinases which exhibit a number of novel properties. Firstly, the phosphate is located on histidine residues within different families of proteins; one kinase(s) utilizes GTP rather than ATP as a phosphate donor and each kinase has its own unique profile of membrane protein phosphorylation (which itself varies with anion species). Secondly, both kinases mediate Cl^–-dependent phosphorylation of an apical membrane protein around the established physiological values for [Cl^–]_i in airway epithelial cells (40 mM); associated phosphatases also alter the net phosphoprotein profile of the apical membrane. These findings are reviewed and their potential roles explored in relation to the pathogenesis of CF using the control of cell volume as a model for disrupted cellular function in CF-affected epithelia.

(Received 16 September 2005; accepted after revision 6 October 2005; first published online 11 October 2005)
Corresponding author A. Mehta: Division of Maternal and Child Health Sciences, University of Dundee, Dundee DD1 9SY, UK. Email: a.mehta{at}dundee.ac.uk

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