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PMID: 3004957 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The B chain of PDGF alone is sufficient for mitogenesis.

The EMBO journal ·Vol. 4 ·No. 13A ·1985-12-16 ·Pages 3399-405

Kelly JD, Raines EW, Ross R, Murray MJ

Abstract

The platelet-derived growth factor (PDGF) is a mitogen derived from human platelets consisting of two related polypeptides termed A and B chains. The entire B chain of PDGF is highly (96%) homologous to a portion of p28sis, the transforming protein of simian sarcoma virus. It has been suggested that p28sis exerts its transforming potential by mimicking the growth promoting activity of PDGF and stimulating the cell in an autocrine manner. We have directly examined the mitogenic potential of p28sis and the B chain homologous region by expressing these heterologous sequences in the yeast Saccharomyces cerevisiae. In our constructions, these proteins are encoded by portions of the v-sis gene. Expression and secretion from the yeast cell is achieved by using a yeast promoter and the alpha-factor pheromone secretory leader. The sis proteins thus expressed and secreted are immunoreactive with anti-PDGF antisera and are mitogenic for cultured fibroblasts. Furthermore, they mediate this mitogenic activity by specific binding to the PDGF cell surface receptor. Gel electrophoresis and cell binding analysis indicates that the mitogenic species is primarily a disulphide-bonded dimer. We are able to conclude that p28sis is a mitogen and that a polypeptide corresponding to the B chain alone is sufficient to account for the mitogenic activity attributed to PDGF.

MeSH Terms
Animals Binding, Competitive Gene Expression Regulation Genetic Vectors Macromolecular Substances Mice Mitogens Oncogene Proteins, Viral/genetics,pharmacology Platelet-Derived Growth Factor/genetics,pharmacology Receptors, Cell Surface/metabolism Receptors, Platelet-Derived Growth Factor Saccharomyces cerevisiae/genetics Structure-Activity Relationship
Chemicals
Macromolecular Substances Mitogens Oncogene Proteins, Viral Platelet-Derived Growth Factor Receptors, Cell Surface Receptors, Platelet-Derived Growth Factor
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kelly J D
Raines E W
Ross R
Murray M J
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44 references, click to expand
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1985-12-16
Pages
3399-405
Language
English
Region
England
NLM ID
8208664
PMCID
PMC554676
Subset
IM
Grants
NHLBI NIH HHS · HL 18645 · United States
External Links
PubMed source PMC Full Text View journal details
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