Saturation of, and competition for entry into, the apical secretory pathway
| Autor: | Firas Rahaal, Enrique Rodriguez-Boulan, Linda Lam, Judit Baffi, Karl G. Csaky, Alan D. Marmorstein |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Vascular Endothelial Growth Factor A
Gene isoform Transgene Genetic Vectors Endothelial Growth Factors Biology Adenoviridae Cell Line chemistry.chemical_compound Transduction Genetic Transforming Growth Factor beta Receptor Secretory pathway chemistry.chemical_classification Lymphokines Multidisciplinary Vascular Endothelial Growth Factors Tunicamycin Lectin Biological Sciences Immunohistochemistry Amino acid Cell biology Gene Expression Regulation chemistry biology.protein Transforming growth factor |
| Zdroj: | Proceedings of the National Academy of Sciences. 97:3248-3253 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.97.7.3248 |
| Popis: | To investigate mechanisms of apical sorting in the secretory pathway of epithelial cells, we expressed varying amounts of the 165 amino acid isoform of vascular endothelial growth factor (VEGF 165 ) and transforming growth factor β1 (TGF-β1) via replication defective adenoviruses. Apical sorting of both proteins was efficient at low expression levels but saturated or was reversed at high expression levels. High expression levels of TGF-β1 were effective at competing VEGF 165 out of the apical pathway; however, VEGF 165 did not compete out TGF-β1. Tunicamycin inhibition experiments showed that the apical polarity of VEGF 165 was independent of N -glycosylation. We conclude that the apical sorting of these two molecules is a saturable, signal-mediated process, involving competition for apical sorting receptors. The sorting of the two proteins does not appear to involve N -glycans as sorting signals, or lectin sorters. The observations are particularly relevant to gene therapy because they demonstrate that overexpression of a transgene can result in undesirable missorting of the encoded protein. |
| Databáze: | OpenAIRE |
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