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Characterization of two monoclonal antibodies reactive with the external domain of the platelet-derived growth factor receptor

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Author

  • Lars Rönnstrand
  • Louis Terracio
  • Lena Claesson-Welsh
  • Carl-Henrik Heldin
  • Kristofer Rubin

Summary, in English

Two monoclonal antibodies against the receptor for platelet-derived growth factor (PDGF) were obtained by immunizing mice with pure PDGF receptor preparations derived from porcine uterus. The antibodies, denoted PDGFR-B1 and PDGFR-B2, both bound to the external domain of the receptor, as demonstrated by indirect immunofluorescence and binding of 125I-labeled antibodies to intact human fibroblasts. Both antibodies precipitated pure 175-kDa 32P-labeled autophosphorylated porcine PDGF receptor as well as a Mr 175,000 glycoprotein from metabolically labeled cells. The monoclonal antibodies did not inhibit binding of 125I-PDGF to human fibroblasts and did not stimulate these cells to undergo mitosis. Both antibodies induced clustering and down-regulation of their antigen. However, this resulted in only a partial loss of cell surface binding sites for PDGF itself, consistent with the conclusion that the monoclonals recognized only one of two or several receptors for PDGF. Clustering and down-regulation were not seen when the cells were incubated with monovalent Fab' fragments of the PDGFR-B2 antibody. The antibodies also stimulated autophosphorylation of pure PDGF receptor, and PDGFR-B2 was shown to stimulate phosphorylation of phosphofructokinase, an exogenous substrate for the PDGF receptor kinase. High concentrations of PDGFR-B2 antibody, or Fab' fragments thereof, failed to enhance the PDGF receptor kinase activity, compatible with the possibility that dimerization was of importance in the antibody-stimulated kinase activity of purified PDGF receptors.

Publishing year

1988

Language

English

Pages

10429-10435

Publication/Series

Journal of Biological Chemistry

Volume

263

Issue

21

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Medicinal Chemistry

Keywords

  • Animals *Antibodies
  • Cell Surface/*immunology/metabolism Receptors
  • Monoclonal Antigen-Antibody Complex Enzyme-Linked Immunosorbent Assay Epitopes/*analysis Female Kinetics Platelet-Derived Growth Factor/metabolism Receptors
  • Platelet-Derived Growth Factor Swine Uterus/metabolism

Status

Published

ISBN/ISSN/Other

  • ISSN: 1083-351X