Deregulated Expression and Function of CFTR and Cl−Secretion after Activation of theRasandSrc/PyMTPathways in Caco-2 Cells
| Autor: | Gisèle Cherqui, Susan E. Davenport, Monique. Mergey, Christian Gespach, Richard C. Boucher, Sherif E. Gabriel |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Transcription Genetic Antigens Polyomavirus Transforming Biophysics Cystic Fibrosis Transmembrane Conductance Regulator Biology Biochemistry chemistry.chemical_compound Adenosine Triphosphate Chlorides Chloride Channels Internal medicine Cyclic AMP medicine Humans Secretion RNA Processing Post-Transcriptional Molecular Biology Protein Kinase C Protein kinase C Forskolin Colforsin Cell Biology Cystic fibrosis transmembrane conductance regulator Cell biology Genes src Genes ras Endocrinology Gene Expression Regulation chemistry Cell culture Phorbol biology.protein Calcium Caco-2 Cells Signal transduction Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Biochemical and Biophysical Research Communications. 229:663-672 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.1996.1861 |
| Popis: | We evaluated the role of the activated Ras and Src/PyMT ( Polyoma Middle T ) signaling pathways on the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in human colonic Caco-2 cell lines. Control vector-transfected Caco-2 cell monolayer preparations (Caco-2-H) responded to forskolin with an increase in short circuit current (I SC ) mediated by CFTR. Furthermore, Caco-2-H cells responded to ATP, a reported stimulator of intracellular Ca 2+ (Ca 2+ i ), and a potential source of adenosine-mediated elevation of cAMP. In contrast, Caco-2 cells transfected with PyMT (Caco-2-MT), expressing high levels of PKC, showed no sustained I SC response to forskolin or ATP. Pretreatment of Caco-2-MT cells with 2.5 μM phorbol 12-myristate 13-acetate (PMA) for 24 hr. effectively down-regulated PKC activity and restored expression of CFTR mRNA but failed to re-establish functional CFTR. These data suggest that, stable up-regulation of PKCα, consequent to activation of the Ras or Src/PyMT pathways, leads to an absence of CFTR expression and Cl − secretion mediated by either cAMP or Ca 2+ i . Moreover, Cl − secretion in the colonic Caco-2 epithelial cell line is mediated primarily by CFTR and an alternate Ca 2+ i -activated Cl − channel is not functional in these cells. |
| Databáze: | OpenAIRE |
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