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CFTR, chloride concentration and cell volume: could mammalian protein histidine phosphorylation play a latent role?

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 ( approximately 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.

journal_name

Exp Physiol

journal_title

Experimental physiology

authors

Treharne KJ,Crawford RM,Mehta A

doi

10.1113/expphysiol.2005.031823

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

131-9

issue

eissn

0958-0670

issn

1469-445X

pii

expphysiol.2005.031823

journal_volume

pub_type

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CFTR, chloride concentration and cell volume: could mammalian protein histidine phosphorylation play a latent role?