Author:
LaRochelle W J,May-Siroff M,Robbins K C,Aaronson S A
Abstract
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.
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
114 articles.
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