|
|
|
|
|
|
|
||
The Journal of Cell Biology, Vol 116, 533-543, Copyright © 1992 by The Rockefeller University Press
ARTICLES |
EW Raines and R Ross
Department of Pathology, University of Washington, Seattle 98195.
The PDGFs are a family of molecules assembled as disulfide-bonded homo- and heterodimers from two distinct but highly homologous polypeptide chains (PDGF-A and PDGF-B). Two PDGF A-chain transcripts, which arise from alternative usage of the 69-bp exon 6 and exon 7, give rise to two forms of PDGF-A. In spite of the conservation of two PDGF A-chain forms over at least 350 million years, no differences in their biological activities have been identified. We have investigated the activity of the sequence encoded by the alternatively spliced exon 6 of the PDGF A- chain (peptide AL). Addition of peptide AL at 10(-5)-10(-9) M to cultured endothelium and smooth muscle induced a dose-dependent, 3-20- fold increase in PDGF in conditioned media within 30 min. Peptide AL had no detectable effect on A- or B-chain transcript levels, and decrease in culture temperature did not prevent rapid release of PDGF. In human umbilical vein endothelial cells treated with peptide AL, the PDGF release was principally PDGF-BB, while in smooth muscle cells it was primarily PDGF-AA. The capacity to induce release of PDGF is shared by the homologous peptide encoded by exon 6 of the B-chain of PDGF. Binding studies and cross-linking analysis are consistent with a charge- based association of exon 6 sequences with membrane- and matrix- associated heparan-sulfate proteoglycans. We hypothesize that translation of exon 6 of the A- or B-chain of PDGF results in compartmentalization of these forms of PDGF with HS-PG, whereas forms lacking this sequence would be soluble and diffuse.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
