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. 1984 Jun;81(11):3424–3428. doi: 10.1073/pnas.81.11.3424

Plasma binding proteins for platelet-derived growth factor that inhibit its binding to cell-surface receptors.

E W Raines, D F Bowen-Pope, R Ross
PMCID: PMC345520  PMID: 6203121

Abstract

Evidence is presented that the binding of platelet-derived growth factor (PDGF) to plasma constituents inhibits the binding of PDGF to its cell-surface mitogen receptor. Approximately equivalent amounts of PDGF-binding activity were found in plasma from a number of different species known by radioreceptor assay to contain PDGF homologues in their clotted blood. Activation of the coagulation cascade did not significantly alter the PDGF-binding activity of the plasma components. Three molecular weight classes of plasma fractions that inhibit PDGF binding to its cell-surface receptor were defined by gel filtration: approximately equal to 40,000, 150,000, and greater than 500,000. Specific binding of 125I-labeled PDGF to the highest molecular weight plasma fraction could also be demonstrated by gel filtration. The binding of PDGF to these plasma components was reversible under conditions of low pH or with guanidine X HCl, and active PDGF could be recovered from the higher molecular weight fractions. Immunologic and functional evidence is presented that the highest molecular weight plasma fraction may be alpha 2-macroglobulin. A model is proposed in which the activity of PDGF released in vivo may be regulated by association with these plasma binding components and by high-affinity binding to cell-surface PDGF receptors.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adham N. F., Chakmakjian Z. H., Mehl J. W., Bethune J. E. Human growth hormone and alpha-2-macroglobulin: a study of binding. Arch Biochem Biophys. 1969 Jun;132(1):175–183. doi: 10.1016/0003-9861(69)90351-8. [DOI] [PubMed] [Google Scholar]
  2. Barrett A. J., Starkey P. M. The interaction of alpha 2-macroglobulin with proteinases. Characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanism. Biochem J. 1973 Aug;133(4):709–724. doi: 10.1042/bj1330709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bernstein L. R., Antoniades H., Zetter B. R. Migration of cultured vascular cells in response to plasma and platelet-derived factors. J Cell Sci. 1982 Aug;56:71–82. doi: 10.1242/jcs.56.1.71. [DOI] [PubMed] [Google Scholar]
  4. Bowen-Pope D. F., Ross R. Platelet-derived growth factor. II. Specific binding to cultured cells. J Biol Chem. 1982 May 10;257(9):5161–5171. [PubMed] [Google Scholar]
  5. Cohen K. L., Nissley S. P. The serum half-life of somatomedin activity: evidence for growth hormone dependence. Acta Endocrinol (Copenh) 1976 Oct;83(2):243–258. doi: 10.1530/acta.0.0830243. [DOI] [PubMed] [Google Scholar]
  6. Grotendorst G. R., Chang T., Seppä H. E., Kleinman H. K., Martin G. R. Platelet-derived growth factor is a chemoattractant for vascular smooth muscle cells. J Cell Physiol. 1982 Nov;113(2):261–266. doi: 10.1002/jcp.1041130213. [DOI] [PubMed] [Google Scholar]
  7. Heldin C. H., Westermark B., Wasteson A. Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3664–3668. doi: 10.1073/pnas.78.6.3664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Huang J. S., Huang S. S., Deuel T. F. Human platelet-derived growth factor: radioimmunoassay and discovery of a specific plasma-binding protein. J Cell Biol. 1983 Aug;97(2):383–388. doi: 10.1083/jcb.97.2.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Huang J. S., Huang S. S., Deuel T. F. Specific covalent binding of platelet-derived growth factor to human plasma alpha 2-macroglobulin. Proc Natl Acad Sci U S A. 1984 Jan;81(2):342–346. doi: 10.1073/pnas.81.2.342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huang J. S., Huang S. S., Kennedy B., Deuel T. F. Platelet-derived growth factor. Specific binding to target cells. J Biol Chem. 1982 Jul 25;257(14):8130–8136. [PubMed] [Google Scholar]
  11. Knauer D. J., Smith G. L. Inhibition of biological activity of multiplication-stimulating activity by binding to its carrier protein. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7252–7256. doi: 10.1073/pnas.77.12.7252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kohler N., Lipton A. Platelets as a source of fibroblast growth-promoting activity. Exp Cell Res. 1974 Aug;87(2):297–301. doi: 10.1016/0014-4827(74)90484-4. [DOI] [PubMed] [Google Scholar]
  13. Nagasawa S., Han B. H., Sugihara H., Suzuki T. Studies on alpha 2-macroglobulin in bovine plasma. II. Interaction of alpha2-macroglobulin and trypsin. J Biochem. 1970 Jun;67(6):821–832. doi: 10.1093/oxfordjournals.jbchem.a129314. [DOI] [PubMed] [Google Scholar]
  14. Raines E. W., Ross R. Platelet-derived growth factor. I. High yield purification and evidence for multiple forms. J Biol Chem. 1982 May 10;257(9):5154–5160. [PubMed] [Google Scholar]
  15. Ronne H., Anundi H., Rask L., Peterson P. A. Nerve growth factor binds to serum alpha-2-macroglobulin. Biochem Biophys Res Commun. 1979 Mar 15;87(1):330–336. doi: 10.1016/0006-291x(79)91683-8. [DOI] [PubMed] [Google Scholar]
  16. Ross R. George Lyman Duff Memorial Lecture. Atherosclerosis: a problem of the biology of arterial wall cells and their interactions with blood components. Arteriosclerosis. 1981 Sep-Oct;1(5):293–311. doi: 10.1161/01.atv.1.5.293. [DOI] [PubMed] [Google Scholar]
  17. Ross R., Glomset J. A. The pathogenesis of atherosclerosis (first of two parts). N Engl J Med. 1976 Aug 12;295(7):369–377. doi: 10.1056/NEJM197608122950707. [DOI] [PubMed] [Google Scholar]
  18. Ross R., Glomset J. A. The pathogenesis of atherosclerosis (second of two parts). N Engl J Med. 1976 Aug 19;295(8):420–425. doi: 10.1056/NEJM197608192950805. [DOI] [PubMed] [Google Scholar]
  19. Ross R., Glomset J., Kariya B., Harker L. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1207–1210. doi: 10.1073/pnas.71.4.1207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ross R., Vogel A. The platelet-derived growth factor. Cell. 1978 Jun;14(2):203–210. doi: 10.1016/0092-8674(78)90107-1. [DOI] [PubMed] [Google Scholar]
  21. Scher C. D., Shepard R. C., Antoniades H. N., Stiles C. D. Platelet-derived growth factor and the regulation of the mammalian fibroblast cell cycle. Biochim Biophys Acta. 1979 Aug 10;560(2):217–241. doi: 10.1016/0304-419x(79)90020-9. [DOI] [PubMed] [Google Scholar]
  22. Senior R. M., Griffin G. L., Huang J. S., Walz D. A., Deuel T. F. Chemotactic activity of platelet alpha granule proteins for fibroblasts. J Cell Biol. 1983 Feb;96(2):382–385. doi: 10.1083/jcb.96.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Seppä H., Grotendorst G., Seppä S., Schiffmann E., Martin G. R. Platelet-derived growth factor in chemotactic for fibroblasts. J Cell Biol. 1982 Feb;92(2):584–588. doi: 10.1083/jcb.92.2.584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Singh J. P., Chaikin M. A., Stiles C. D. Phylogenetic analysis of platelet-derived growth factor by radio-receptor assay. J Cell Biol. 1982 Nov;95(2 Pt 1):667–671. doi: 10.1083/jcb.95.2.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Westermark B., Wasteson A. A platelet factor stimulating human normal glial cells. Exp Cell Res. 1976 Mar 1;98(1):170–174. doi: 10.1016/0014-4827(76)90476-6. [DOI] [PubMed] [Google Scholar]
  26. Williams L. T., Tremble P., Antoniades H. N. Platelet-derived growth factor binds specifically to receptors on vascular smooth muscle cells and the binding becomes nondissociable. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5867–5870. doi: 10.1073/pnas.79.19.5867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zapf J., Froesch E. R., Humbel R. E. The insulin-like growth factors (IGF) of human serum: chemical and biological characterization and aspects of their possible physiological role. Curr Top Cell Regul. 1981;19:257–309. doi: 10.1016/b978-0-12-152819-5.50024-5. [DOI] [PubMed] [Google Scholar]
  28. Zapf J., Schoenle E., Jagars G., Sand I., Grunwald J., Froesch E. R. Inhibition of the action of nonsuppressible insulin-like activity on isolated rat fat cells by binding to its carrier protein. J Clin Invest. 1979 May;63(5):1077–1084. doi: 10.1172/JCI109377. [DOI] [PMC free article] [PubMed] [Google Scholar]

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