| Autor: |
Graham, W. Vallen, Yingmin Wang, Schwarz, Brad T., Marchiando, Amanda M., Turner, Jerrold R. |
| Předmět: |
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| Zdroj: |
FASEB Journal; Apr2007, Vol. 21 Issue 5, pA587-A587, 1/5p |
| Abstrakt: |
Two myosin light chain kinase (MLCK) isoforms, MLCK1 and MLCK2, which differ only by a short insertion in MLCK1 are expressed in intestinal epithelia. MLCK1 localizes to the perijunctional actomyosin ring and tight junction while MLCK2 is distributed more diffusely. We have previously shown that intestinal epithelial MLCK is transcriptionally and enzymatically activated by TNF, both in vitro and in vivo, and that this upregulation is critical to TNF-induced barrier dysfunction. Since MLCK1 regulates epithelial barrier function, we hypothesized that TNF might specifically upregulate MLCK1 transcription or targeting to the perijunctional actomyosin ring. MLCK1 and total MLCK were detected using PCR primers or antibodies directed against the unique MLCK1 insertion or regions shared by both isoforms, respectively. Real-time RT PCR analysis of Caco-2 monolayers showed that MLCK1 and total MLCK mRNA transcripts increased 4.1- and 3.5-fold, respectively, 4 hours after TNF treatment. Immunofluorescence microscopy demonstrated concomitant recruitment of MLCK1 to the perijunctional actomyosin ring. TNF caused similar MLCK1 recruitment to the perijunctional actomyosin ring of murine enterocytes in vivo. These data demonstrate that TNF upregulates MLCK1 expression and, perhaps more importantly, that TNF enhances MLCK1 targeting to the perijunctional actomyosin ring in vitro and in vivo. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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