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Platelet-derived Growth Factor and its Role in Mitogenesis and Transformation

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Book cover Cell to Cell Signals in Mammalian Development

Part of the book series: NATO ASI Series ((ASIH,volume 26))

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Abstract

Human platelet-derived growth factor (PDGF) is an Mr 30,000 protein made up as dimers of A and B chains (Johnsson et al. 1982) which are encoded by separate genes (Betsholtz et al. 1986a and references therein). The two chains are synthesized as prepropeptides that are processed by dimerization and proteolytic cleavage. Within the amino acid sequences of the mature chains, there is a 60% amino acid sequence homology indicating that the two genes have evolved through gene duplication and evolutionary divergence. The possible evolutionary advantage of the development of two closely related PDGF genes is not understood. However, it has recently become evident that all three possible dimeric forms of PDGF exist and that they may display differences in their functional activities.

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References

  • Barrett TB, Gajdusek CM, Schwartz SM, McDougall JK, Benditt EP (1985) Expression of the sis gene by endothelial cells in culture and in vivo. Proc Natl Acad Sci USA 81:6772–6774

    Article  Google Scholar 

  • Betsholtz C, Johnsson A, Heldin C-H, Westermark B, Lind P, Urdea MS, Eddy R, Shows TB, Philpott K, Mellor AL, Knott TJ, Scott J (1986a) cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumor cell lines. Nature 320:695–699

    Article  PubMed  CAS  Google Scholar 

  • Bywater M, Rorsman F, Bongcam-Rudloff E, Mark G, Heldin C-H, Westermark B, Betsholtz C (1988) Expression of recombinant PDGF A and B chain homodimers in Rat 1 cells and human fibroblasts reveals differences in protein processing and autocrine effects. Submitted

    Google Scholar 

  • Betsholtz C, Johnsson A, Heldin C-H, Westermark B (1986) Efficient reversion of SSV-transformat ion and inhibition of growth factor-induced mitogenesis by suramin. Proc Natl Acad Sci USA 83:6440–6444

    Article  PubMed  CAS  Google Scholar 

  • Deinhardt F (1980) The biology of primate retroviruses. In Klein G (ed) Viral Oncology. New York Raven Press pp 359–398

    Google Scholar 

  • Devare SG, Reddy EP, Law JD, Robbins KC, Aaronson SA (1983) Nucleotide sequence of the simian sarcoma virus genome: demonstration that its acquired cellular sequences encode the transformation gene product p28 sis. Proc Natl Acad Sci USA 80:731–735

    Article  PubMed  CAS  Google Scholar 

  • Dicorleto PE, Bowen-Pope DF (1983) Cultured endothelial cells produce a platelet-derived growth factor-like protein. Proc Natl Acad Sci USA 80:1919–192

    Article  PubMed  CAS  Google Scholar 

  • Doolittle RF, Hunkapiller MW, Hood LE, Devare SG, Robbins KC, Aaronson SA, Antoniades HN (1983) Simian sarcoma virus oncogene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science 221:275–277

    Article  PubMed  CAS  Google Scholar 

  • Goustin AS, Betsholtz C, Pfeifer-Ohlsson S, Persson H, Rydnert J, Bywater M, Holmgren G, Heldin C-H, Westermark B, Ohlsson R (1985) Co-expression of sis and myc proto—oncogenese in human placenta suggest autocrine control of trophoblast growth. Cell 41:301–312

    Article  PubMed  CAS  Google Scholar 

  • Hammacher A, Hellman U, Johnsson A, Östman A, Gunnarsson K, Westermark B, Wasteson A, Heldin C-H (1988a) PDGF purified from human platelets is a heterodimer of one A and one B chain. Submitted

    Google Scholar 

  • Hammacher A, Nistér M, Westermark B, Heldin C-H (1988b) A human glioma cell line secretes three structurally and functionally different dimeric forms of PDGF. Submitted

    Google Scholar 

  • Heldin C-H, Johnsson A, Wennergren S, Wernstedt C, Betsholtz C, Westermark B (1986) A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A chains. Nature 319–514

    Article  Google Scholar 

  • Heldin C-H, Betsholtz C, Claesson-Welsh L, Westermark B (1987) Subversion of growth regulatoy pathways in malignant transformation. Biochim Biophys Acta 907:219–244

    PubMed  CAS  Google Scholar 

  • Heldin C-H, Bäckström G, Östman A, Hammacher A, Rönnstrand L, Rubin K, Nistér M, Westermark B (1988) Different dimeric forms of PDGF differ in binding to separate receptors on human fibroblasts. Submitted

    Google Scholar 

  • Johnsson A, Heldin C-H, Wasteson A, Westermark B, Deuel TF, Huang JS, Seeburg PH, Gray A, Ullrich A, Scrace G, Stroobant P, Waterfield MD (1984) The c-sis gene encodes a precursor of B chain of platelets—derived growth factor. EMBO J 3:921–928

    PubMed  CAS  Google Scholar 

  • Johnsson A, Betsholtz C, Heldin C-H, Westermark B (1985) Antobodies against platelet-derived growth factor inhibit acute transformation by simian sarcoma virus.Nature 317:438–440

    Article  PubMed  CAS  Google Scholar 

  • Johnsson A, Betsholtz C, Heldin C-H, Westermark B (1986) The phenotypic characteristics of simian sarcoma virus-transformed human fibroblasts suggest that the v-sis gene product acts solely as a PDGF receptor agonist in cell transformation. EMBO J 5:1535–1541

    PubMed  CAS  Google Scholar 

  • Josephs SF, Ratner L, Clarke MF, Westin EH, Reitz MS, Wong-Staal F (1984) Transforming potential of human c-sis nucleotide sequences encoding platelet-derived growth factor. Sience 225:636–639

    Article  CAS  Google Scholar 

  • King CR, Giese NA, Robbins KC, Aaronson SA (1985) In vitro mutagenesis of the v-sis transforming gene defines functional domains of its growth factor=related product. Proc Natl Acad Sci USA 82:5295–5299

    Article  PubMed  CAS  Google Scholar 

  • Laker C, Stocking C, Bergholz U, Hess N, De Lamarter JF, Ostertag W (1987) Autocrine stimulation after transfer of the granulocyte/macrophage colony-stimulating factor gene and autonomous growth are distinct but independent steps in the oncogenic pathway. Proc Natl Sci USA 84:8458–8462

    Article  CAS  Google Scholar 

  • Leal F, Williams LT, Robbins KC, Aaronson KC (1985) Evidence that the v-sis gene product transforms by interaction with the receptor for platelet-derived growth factor. Science 230:327–330

    Article  PubMed  CAS  Google Scholar 

  • Martinet Y, Bitterman PB, Mornex J-F, Grotendorst G, Martin GR, Crystal RG (1986) Activated human monocytes express the c-sis proto—oncogene and release a mediator showing PDGF-like activity. Nature 319:158–160

    Article  PubMed  CAS  Google Scholar 

  • Nistér M, Libermann T, Betsholtz C, Pettersson M, Claesson-Welsh L, Heldin C-H, Schlessinger J, Westermark B (1988a) Expression of messenger RNAs for platelet-derived growth factor and transforming growth factor-α and their receptors in human malignant glioma cell lines. Cancer Res in press

    Google Scholar 

  • Nistér M, Hammacher A, Mellström K, Siegbahn A, Rönnstrand L, Westermark B, Heldin C-H (1988b) A glioma-derived PDGF A chain homodimer has different functional activities than a PDGF AB heterodimer purified from human platelets. Cell in press

    Google Scholar 

  • Paulsson Y, Hammacher A, Heldin C-H, Westermark B (1987) Possible autocrine feedback in the prereplicative phase of human fibroblasts. Nature 328:715–717

    Article  PubMed  CAS  Google Scholar 

  • Peres R, Betsholtz C, Westermark B, Heldin C-H (1987) Frequent expression for growth factors for mesenchymal cells in human mammary carcinoma. Cancer Res 47:3425–3429

    PubMed  CAS  Google Scholar 

  • Rao CD, Igarashi H, Chiu I-M, Robbins KC, Aaronson SA (1986) Structure and sequence of the human c-sis/platelets-derived growth factor 2 (SIS/PDGF 2) transcriptional unit. Proc Natl Acad Sci USA 83:2392–2396

    Article  PubMed  CAS  Google Scholar 

  • Rao CD, Pech M, Robbins KC, Aaronson SA (1988) The 5′ untranslated sequence of c-sis/platelet—derived growth factor 2 transcript is a potent translational inhibitor. Mol Cell Biol 8:284–292

    PubMed  CAS  Google Scholar 

  • Richardson WD, Pringle N, Mosley MJ, Westermark B, Dubois-Dalcq M (1988) A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell in press

    Google Scholar 

  • Robbins KC, Antoniades HN, Devare SG, Hunkapiller MW, Aaronson SA (1983) Structural and immunological similarities between simian sarcoma virus gene product(s) and human platelet-derived growth factor. Nature 305:605–608

    Article  PubMed  CAS  Google Scholar 

  • Rorsman F, Bywater M, Knott TJ, Scott J, Betsholtz C (1988) Structural characterization of the human platelet-derived growth factor A-chain cDNA and gene: alternative exon usage predicts two different precursor proteins. Mol Cell Biol in press

    Google Scholar 

  • Seifert RA, Schwartz SM, Bowen-Pope DF (1984) Developmentally regulated production of platelet-derived growth factor—like molecules. Nature 311:669–671

    Article  PubMed  CAS  Google Scholar 

  • Shimokado K, Raines EW, Madtes DK, Barrett TB, Benditt EP, Ross RA (1985) A significant part of macrophage—derived growth factor consists of at least two forms of PDGF. Cell 43:277–286

    Article  PubMed  CAS  Google Scholar 

  • Stroobant P, Waterfield MD (1983) Purification and properties of porcine platelet-derived growth factor EMBO J 3:2963–2967

    Google Scholar 

  • Waterfield MD, Scrace GT, Whittle N, Stroobant P, Johnsson A, Wasteson A, Westermark B, Heldin C-H, Huang JS, Deuel TF (1983) Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature 304:35–39

    Article  PubMed  CAS  Google Scholar 

  • Westermark B, Johnsson A, Paulsson Y, Betsholtz C, Heldin C-H, Herlyn M, Rodeck U, Koprowski H (1986) Human melanoma cells of primary and metastatic origin express the genes encoding the constituent chains of PDGF and produce a PDGF-like growth factor. Proc Natl Acad USA 83:7197–7200

    Article  CAS  Google Scholar 

  • Westermark B, Betsholtz C, Johnsson A, Heldin C-H (1987) Acute transformation by simian sarcoma virus is mediated by an externalized PDGF-like growth factor. In Viral Carcinogenesis. Kjeldgard NO, Forchhammer J (eds) Munksgaard, Copenhagen, pp 445–457.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Dept. of Pathology, University Hospital, S-751 85, Uppsala, Sweden

    B. Westermark

  2. Ludwig Institute for Cancer Research, Biomedical Center, Box 595, S-751 23, Uppsala, Sweden

    C.-H. Heldin

Authors
  1. B. Westermark
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  2. C.-H. Heldin
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Editor information

Editors and Affiliations

  1. Hubrecht Laboratory, The Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands

    S. W. de Laat , J. G. Bluemink  & C. L. Mummery ,  & 

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© 1989 Springer-Verlag Berlin Heidelberg

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Westermark, B., Heldin, CH. (1989). Platelet-derived Growth Factor and its Role in Mitogenesis and Transformation. In: de Laat, S.W., Bluemink, J.G., Mummery, C.L. (eds) Cell to Cell Signals in Mammalian Development. NATO ASI Series, vol 26. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73142-6_21

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  • DOI: https://doi.org/10.1007/978-3-642-73142-6_21

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73144-0

  • Online ISBN: 978-3-642-73142-6

  • eBook Packages: Springer Book Archive

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