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

Resultado de la investigación: Article

73 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)271-281
Número de páginas11
PublicaciónGrowth Factors
Volumen1
N.º3
DOI
EstadoPublished - 1 ene 1989

Huella dactilar

Platelet-Derived Growth Factor
Yeast
Saccharomyces cerevisiae
Protein Isoforms
Fibroblasts
Proto-Oncogene Proteins c-sis
Platelet-Derived Growth Factor Receptors
Structural analysis
Dimers
Agar
Yeasts
Cells
platelet-derived growth factor BB
Growth

ASJC Scopus subject areas

  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Citar esto

Östman, Arne ; Bäckström, Gudrun ; Fong, Noel ; Betsholtz, Christer ; Wernstedt, Christer ; Hellman, Ulf ; Westermark, Bengt ; Valenzuela, Pablo ; Heldin, Carl Henrik. / Expression of three recombinant homodimeric isoforms of PDGF in saccharomyces cerevisiae : Evidence for difference in receptor binding and functional activities. En: Growth Factors. 1989 ; Vol. 1, N.º 3. pp. 271-281.
@article{f02d9fd67ec54068bfcfceb6f600cd5c,
title = "Expression of three recombinant homodimeric isoforms of PDGF in saccharomyces cerevisiae: Evidence for difference in receptor binding and functional activities",
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.",
keywords = "Isoforms, PDGF, Yeast expression",
author = "Arne {\"O}stman and Gudrun B{\"a}ckstr{\"o}m and Noel Fong and Christer Betsholtz and Christer Wernstedt and Ulf Hellman and Bengt Westermark and Pablo Valenzuela and Heldin, {Carl Henrik}",
year = "1989",
month = "1",
day = "1",
doi = "10.3109/08977198908998003",
language = "English",
volume = "1",
pages = "271--281",
journal = "Growth Factors",
issn = "0897-7194",
publisher = "Informa Healthcare",
number = "3",

}

Östman, A, Bäckström, G, Fong, N, Betsholtz, C, Wernstedt, C, Hellman, U, Westermark, B, Valenzuela, P & Heldin, CH 1989, 'Expression of three recombinant homodimeric isoforms of PDGF in saccharomyces cerevisiae: Evidence for difference in receptor binding and functional activities', Growth Factors, vol. 1, n.º 3, pp. 271-281. https://doi.org/10.3109/08977198908998003

Expression of three recombinant homodimeric isoforms of PDGF in saccharomyces cerevisiae : Evidence for difference in receptor binding and functional activities. / Östman, Arne; Bäckström, Gudrun; Fong, Noel; Betsholtz, Christer; Wernstedt, Christer; Hellman, Ulf; Westermark, Bengt; Valenzuela, Pablo; Heldin, Carl Henrik.

En: Growth Factors, Vol. 1, N.º 3, 01.01.1989, p. 271-281.

Resultado de la investigación: Article

TY - JOUR

T1 - Expression of three recombinant homodimeric isoforms of PDGF in saccharomyces cerevisiae

T2 - Evidence for difference in receptor binding and functional activities

AU - Östman, Arne

AU - Bäckström, Gudrun

AU - Fong, Noel

AU - Betsholtz, Christer

AU - Wernstedt, Christer

AU - Hellman, Ulf

AU - Westermark, Bengt

AU - Valenzuela, Pablo

AU - Heldin, Carl Henrik

PY - 1989/1/1

Y1 - 1989/1/1

N2 - 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.

AB - 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.

KW - Isoforms

KW - PDGF

KW - Yeast expression

UR - http://www.scopus.com/inward/record.url?scp=0024339109&partnerID=8YFLogxK

U2 - 10.3109/08977198908998003

DO - 10.3109/08977198908998003

M3 - Article

VL - 1

SP - 271

EP - 281

JO - Growth Factors

JF - Growth Factors

SN - 0897-7194

IS - 3

ER -