Accumulating evidence suggests that protein-protein interactions play an important role in transepithelial ion transport. In the present study, we report on the biochemical and functional association between cystic fibrosis transmembrane conductance regulator (CFTR) and a PDZ domain-containing protein Shank2. Exploratory reverse transcription-PCR screening revealed mRNAs for several members of PDZ domain-containing proteins in epithelial cells. Shank2, one of these scaffolding proteins, showed a strong interaction with CFTR by yeast two-hybrid assays. Shank2-CFTR interaction was verified by co-immunoprecipitation experiments in mammalian cells. Notably, this interaction was abolished by mutations in the PDZ domain of Shank2. Protein phosphorylation, HCO 3 ؊ transport and Cl ؊ current by CFTR were measured in NIH 3T3 cells with heterologous expression of Shank2. Of interest, expression of Shank2 suppressed cAMP-induced phosphorylation and activation of CFTR. Importantly, loss of Shank2 by stable transfection of antisense-hShank2 plasmid strongly increased CFTR currents in colonic T84 cells, in which CFTR and Shank2 were natively expressed. Our results indicate that Shank2 negatively regulates CFTR and that this may play a significant role in maintaining epithelial homeostasis under normal and diseased conditions such as those presented by secretory diarrhea.Secretory epithelia perform vectorial transport of salt and water molecules by coordinated actions of the transporters expressed in polarized epithelial membranes. One of the key membrane proteins regulating overall fluid movements is the cystic fibrosis transmembrane conductance regulator (CFTR), 1 which itself has an anion-transporting activity (1-3). Aberrant membrane transport caused by either hypo-or hyper-functioning of CFTR, can be detrimental, and may result in life-threatening diseases, such as cystic fibrosis or secretory diarrhea (4, 5). Therefore, the fine regulation of salt and water transport is essential in epithelial and body homeostasis.Accumulating evidence suggests that protein-protein interaction performs an important role in the regulation of transepithelial ion transport (6). Clustering of ion transporters and associated proteins in microdomains of polarized epithelia can facilitate the effective secretion or absorption of salt and water molecules. In this regard, modular adaptor proteins such as PDZ (PSD-95/discs large/ZO-1) domain-containing proteins have drawn increasing attention due to their ability to form supramolecular complexes (7). We have previously shown that the regulatory interaction between CFTR and Na ϩ /H ϩ exchanger 3 (NHE3) through PDZ-based scaffolds is essential for the coordinated regulation of pancreatic bicarbonate secretion (8). In addition, it was found that a number of membrane transporters and receptors participating in pancreatic fluid formation, such as Na ϩ -HCO 3 Ϫ cotransporters (NBC), purinergic receptors, and secretin receptors have a PDZ-binding motif on their C terminus (9, 10). Therefore, multiple pro...
Objectives: The aim of this study was to evaluate the relationship of occupational stress and psychosocial stress to health promotion behaviors depending on characteristics of female office workers and emotional labor workers for sales. Methods: A survey of 207 female service workers engaging in sales of cosmetics in major department stores and 149 females working in the offices of cosmetics companies was carried out using a self-administered questionnaire. Results: It showed a significant difference in job demand and insufficient job control which are sub-domains of stress. The percentage of emotional laborers exposed to a high risk of psychosocial stress was higher than office workers. In office workers, occupational stress stemmed from insufficient job control and low reward of work was significantly related to psychosocial stress. But in emotional labor workers, stress from job insecurity, and organizational system were added. The relevant factors that affect health promotion behaviors were type of occupational stress, psychosocial stress, marital status, educational level and working career. Conclusions: Occupational stress and psychosocial stress were closely associated with health promotion behaviors. It was suggested that the development of health promotion programs which reduce the stress in female office and emotional labor workers.
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