Protein Kinase Cδ Regulates Airway Mucin Secretion via Phosphorylation of MARCKS Protein
| Autor: | Joungjoa Park, William R. Lampe, Jin-Ah Park, Anne L. Crews, Kenneth B. Adler, Shijing Fang |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Bryostatin 1
Bronchi Biology Pathology and Forensic Medicine Cell Line chemistry.chemical_compound Humans Secretion Benzopyrans MARCKS Phosphorylation Protein kinase A Myristoylated Alanine-Rich C Kinase Substrate Protein Kinase Inhibitors Protein kinase C Mucin Intracellular Signaling Peptides and Proteins Mucins Acetophenones Membrane Proteins Epithelial Cells Bryostatins Cell biology Enzyme Activation Protein Kinase C-delta chemistry Biochemistry Tetradecanoylphorbol Acetate Rottlerin Regular Articles |
| Popis: | 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 delta-isoform (PKC delta). Here, we further investigated the role of PKC delta 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 delta-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 delta activator bryostatin 1. A dominant-negative PKC delta construct (pEGFP-N1/PKC delta 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 delta and enhanced mucin secretion and MARCKS phosphorylation. Similar transfections of a dominant-negative or wild-type PKC epsilon construct did not affect either mucin secretion or MARCKS phosphorylation. The results suggest that PKC delta plays an important role in mucin secretion by airway epithelium via regulation of MARCKS phosphorylation. |
| Databáze: | OpenAIRE |
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