Expression of three recombinant homodimeric isoforms of PDGF in saccharomyces cerevisiae: Evidence for difference in receptor binding and functional activities

Arne Östman, Gudrun Bäckström, Noel Fong, Christer Betsholtz, Christer Wernstedt, Ulf Hellman, Bengt Westermark, Pablo Valenzuela, Carl Henrik Heldin

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

Abstract

Three recombinant homodimeric isoforms of platelet-derived growth factor (PDGF) were produced and purified in milligram quantities by expression of PDGF A-and B-chains in yeast cells. Structural analysis of the purified short and long variants of PDGF-AA (PDGF-AAS and PDGF-AAL) and PDGF-BB showed that they had been properly processed and assembled into dimers. PDGF-AAs and PDGF-AAL were found to bind only to the PDGF A-type receptor on human fibroblasts, with affinities of 0.1 and 0.2 uM, respectively. PDGF-BB bound to cells with A-and B-type receptors and to cells with B-type receptor only with affinities of 0.6 nM in both cases. Each fibroblast appeared to express about 4-5 times more B-type receptors than A-type receptors. The maximal mitogenic response to PDGF-BB of human fibroblasts was almost 2-fold higher than that induced by either of the two PDGF-AA forms. The three isoforms of PDGF also stimulated growth in soft agar of human fibroblasts with PDGF-BB inducing a higher maximal response.

Original languageEnglish
Pages (from-to)271-281
Number of pages11
JournalGrowth Factors
Volume1
Issue number3
DOIs
Publication statusPublished - 1 Jan 1989

Keywords

  • Isoforms
  • PDGF
  • Yeast expression

ASJC Scopus subject areas

  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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