Published online before print November 30, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070318

Accepted for publication September 10, 2007.

Article

Protein Kinase C Regulates Airway Mucin Secretion via Phosphorylation of MARCKS Protein

Jin-Ah Park^*, Anne L. Crews^*, William R. Lampe^*, Shijing Fang^*, Joungjoa Park^*, and Kenneth B. Adler^*@

From the Department of Molecular Biomedical Sciences,* College of Veterinary Medicine, and the Department of Environmental and Molecular Toxicology, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, North Carolina

^@ To whom correspondence should be addressed. E-mail: kenneth_adler{at}ncsu.edu.

	Abstract

Mucin hypersecretion is a major pathological feature of many respiratory diseases, yet cellular mechanisms regulating secretion of mucin have not been fully elucidated. Previously, we reported that mucin hypersecretion induced by human neutrophil elastase involves activation of protein kinase C (PKC), specifically the -isoform (PKC). Here, we further investigated the role of PKC in mucin hypersecretion using both primary human bronchial epithelial cells and the human bronchial epithelial 1 cell line as in vitro model systems. Phorbol-12-myristate-13-acetate (PMA)-induced mucin hypersecretion was significantly attenuated by rottlerin, a PKC-selective inhibitor. Rottlerin also reduced PMA- or human neutrophil elastase-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) protein in these cells. Both secretion and MARCKS phosphorylation were significantly enhanced by the PKC activator bryostatin 1. A dominant-negative PKC construct (pEGFP-N1/PKC^K376R) transfected into human bronchial epithelial 1 cells significantly attenuated both PMA-induced mucin secretion and phosphorylation of MARCKS, whereas transfection of a wild-type construct increased PKC and enhanced mucin secretion and MARCKS phosphorylation. Similar transfections of a dominant-negative or wild-type PKC construct did not affect either mucin secretion or MARCKS phosphorylation. The results suggest that PKC plays an important role in mucin secretion by airway epithelium via regulation of MARCKS phosphorylation.