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A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains

Nature volume 319, pages 511–514 (1986)Cite this article

Abstract

Platelet-derived growth factor (PDGF), as purified from fresh human platelets, is a protein of relative molecular mass (Mr) 30,000 composed of two disulphide-linked subunit chains of similar size, named A and B (ref. 1). The dimer structure of PDGF seems to be important for its biological effects, as reduction irreversibly inactivates the factor; it is not known, however, whether PDGF exists as a heterodimer or as a mixture of homodimers. Amino-acid sequence analysis has revealed that the A- and B-chains of human PDGF are related to each other, and that the B-chain is almost identical to part of the v-sis gene product of simian sarcoma virus (SSV)2–5. There is experimental evidence that a PDGF-like protein is indeed operational in SSV-induced transformation6–12 and the biologically active v-sis product is probably structurally similar to a putative dimer of PDGF B-chains13. PDGF-like growth factors and/or a 4.2-kilobase (kb) c-sis transcript are present in several transformed mammalian cell lines7,14–24 and in certain nontrans-formed cells25–30; cloned c-sis complementary DNA from human T cells transformed with human T-lymphotropic virus (HTLV)24,31 or from human endothelial cells32 contains the coding sequence for a putative PDGF B-chain precursor, but apparently lacks PDGF A-chain sequences. We have previously partially purified and characterized a PDGF-like growth factor from U-2 OS cells (osteosarcoma-derived growth factor, ODGF) and shown that this factor has structural, functional and immunological characteristics in common with PDGF14. We describe here a procedure for the preparation of homogeneous ODGF, and provide evidence that this factor, which binds to the PDGF receptor, has a structure similar to a homodimer of PDGF A-chains.

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Authors and Affiliations

  1. Department of Medical and Physiological Chemistry, Biomedicum, Box 575, S-751 23, Uppsala, Sweden

    Carl-Henrik Heldin, Ann Johnsson, Suzanne Wennergren & Christer Wernstedt

  2. Department of Pathology, University Hospital, S-751 85, Uppsala, Sweden

    Christer Betsholtz & Bengt Westermark

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  1. Carl-Henrik Heldin
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  2. Ann Johnsson
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  6. Bengt Westermark
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Heldin, CH., Johnsson, A., Wennergren, S. et al. A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains. Nature 319, 511–514 (1986). https://doi.org/10.1038/319511a0

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