Published ahead of print on February 2, 2006, doi:10.1165/rcmb.2005-0442OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2005-0442OC Regulation of the ClC-2 Lung Epithelial Chloride Channel by Glycosylation of SP1Eudowood Divison of Pediatric Respiratory Sciences, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland Correspondence and requests for reprints should be addressed to Pamela L. Zeitlin, M.D., Ph.D., Department of Pediatrics, The Johns Hopkins University School of Medicine, Park 316, 600 N. Wolfe St, Baltimore, MD 21287. E-mail: pzeitlin{at}jhmi.edu Chloride channel–2 (ClC-2) is a pH- and voltage-activated chloride channel that is highly expressed in mammalian fetal airway epithelia during the period of maximal fluid secretion. A high level of luminal ClC-2 protein expression is maintained by the SP1 transcription factor until SP1 and ClC-2 decline rapidly at birth. Using fetal (preII-19) and adult (L2) rat lung Type 2 cell lines, we demonstrate that the active higher-molecular-weight 105-kD isoform of SP1 is phosphorylated and glycosylated. Exposure of either cell line to high-dose glutamine is sufficient to induce glycosylation of SP1 and to induce and maintain ClC-2. Exposure to tunicamycin to inhibit SP1 glycosylation reduces ClC-2 expression. We also demonstrate that in vivo ClC-2 expression is similarly regulated. SP1 from 6-wk-old murine lung (high ClC-2 expression) is hyperphosphorylated and hyperglycosylated compared with SP1 from 16–wk-old lung (low ClC-2 expression). Our results support the hypothesis that glycosylation of SP1 produces the 105-kD isoform of SP1 and is involved in regulating ClC-2 gene expression.
Key Words: chloride channel • transcription factor • cystic fibrosis • mouse • lung development This article has been cited by other articles:
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