Saturation of, and competition for entry into, the apical secretory pathway Academic Article uri icon

Overview

MeSH Major

  • Endothelial Growth Factors
  • Gene Expression Regulation
  • Lymphokines
  • Transforming Growth Factor beta

abstract

  • 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 beta1 (TGF-beta1) 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-beta1 were effective at competing VEGF(165) out of the apical pathway; however, VEGF(165) did not compete out TGF-beta1. 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.

publication date

  • March 28, 2000

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC16224

Digital Object Identifier (DOI)

  • 10.1073/pnas.070049497

PubMed ID

  • 10725401

Additional Document Info

start page

  • 3248

end page

  • 53

volume

  • 97

number

  • 7