A novel mechanism regulating growth factor association with the cell surface : identification of a PDGF retention domain
Platelet-derived growth factor (PDGF) chimeras were used to map a domain responsible for either efficient secretion of PDGF-A or the tight cell association of PDGF-B to their carboxy-terminal domains. Introduction of stop codons within PDGF-A or PDGF-B further dissected their respective carboxy-term...
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Veröffentlicht in: | Genes & development 1991-07, Vol.5 (7), p.1191-1199 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Platelet-derived growth factor (PDGF) chimeras were used to map a domain responsible for either efficient secretion of PDGF-A or the tight cell association of PDGF-B to their carboxy-terminal domains. Introduction of stop codons within PDGF-A or PDGF-B further dissected their respective carboxy-terminal domains. Although successive deletions of the PDGF-A carboxyl terminus did not impair its secretion, incremental deletions from the carboxyl terminus of PDGF-B abrogated its membrane retention properties and promoted secretion. By this approach, PDGF-B retention properties could be localized to PDGF-B residues 212-226. A processed form of PDGF-B, which contained this domain, was expressed at the cell surface but not released. Comparison of PDGF-B with PDGF-A revealed an analogous sequence located at the PDGF-A carboxyl terminus. We demonstrated that this PDGF-A domain also acts as a retention sequence under conditions that inhibit its proteolytic cleavage. Thus, differences in PDGF-A and PDGF-B secretion relate to differential proteolytic processing of analogous retention domains. All of these findings establish a new mechanism for stable growth factor presentation at the cell surface. |
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ISSN: | 0890-9369 1549-5477 |
DOI: | 10.1101/gad.5.7.1191 |