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. 1983 Mar 1;96(3):679–683. doi: 10.1083/jcb.96.3.679

Interactions between the receptors for platelet-derived growth factor and epidermal growth factor

PMCID: PMC2112417  PMID: 6300138

Abstract

Preincubation of Swiss 3T3 cells or human fibroblasts with purified platelet-derived growth factor (PDGF) at 4 degrees C or 37 degrees C rapidly inhibits subsequent binding of 125I-epidermal growth factor (125I-EGF). The effect does not result from competition by PDGF for binding to the EGF receptor since (a) very low concentrations of PDGF are effective, (b) cells with EGF receptors but no PDGF receptors are not affected, and (c) the inhibition persists even if the bound PDGF is eluted before incubating the cells with 125I-EGF. PDGF does not affect 125I-insulin binding nor does EGF affect 125I-PDGF binding under these conditions. Endothelial cell-derived growth factor also competes for binding to PDGF receptors and inhibits 125I-EGF binding. The inhibition demonstrated by PDGF seems to result from an increase in the Kd for 125I-EGF binding with no change in the number of EGF 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. Anderson R. G., Goldstein J. L., Brown M. S. Localization of low density lipoprotein receptors on plasma membrane of normal human fibroblasts and their absence in cells from a familial hypercholesterolemia homozygote. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2434–2438. doi: 10.1073/pnas.73.7.2434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker J. B., Barsh G. S., Carney D. H., Cunningham D. D. Dexamethasone modulates binding and action of epidermal growth factor in serum-free cell culture. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1882–1886. doi: 10.1073/pnas.75.4.1882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Brown K. D., Dicker P., Rozengurt E. Inhibition of epidermal growth factor binding to surface receptors by tumor promotors. Biochem Biophys Res Commun. 1979 Feb 28;86(4):1037–1043. doi: 10.1016/0006-291x(79)90221-3. [DOI] [PubMed] [Google Scholar]
  5. Carpenter G., Cohen S. 125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts. J Cell Biol. 1976 Oct;71(1):159–171. doi: 10.1083/jcb.71.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carpenter G., King L., Jr, Cohen S. Epidermal growth factor stimulates phosphorylation in membrane preparations in vitro. Nature. 1978 Nov 23;276(5686):409–410. doi: 10.1038/276409a0. [DOI] [PubMed] [Google Scholar]
  7. Carpenter G., King L., Jr, Cohen S. Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor. J Biol Chem. 1979 Jun 10;254(11):4884–4891. [PubMed] [Google Scholar]
  8. Carpenter G. Solubilization of membrane receptor for epidermal growth factor. Life Sci. 1979 Apr 30;24(18):1691–1697. doi: 10.1016/0024-3205(79)90254-6. [DOI] [PubMed] [Google Scholar]
  9. Chait A., Ross R., Albers J. J., Bierman E. L. Platelet-derived growth factor stimulates activity of low density lipoprotein receptors. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4084–4088. doi: 10.1073/pnas.77.7.4084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clemmons D. R., Van Wyk J. J., Pledger W. J. Sequential addition of platelet factor and plasma to BALB/c 3T3 fibroblast cultures stimulates somatomedin-C binding early in cell cycle. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6644–6648. doi: 10.1073/pnas.77.11.6644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cohen P. The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature. 1982 Apr 15;296(5858):613–620. doi: 10.1038/296613a0. [DOI] [PubMed] [Google Scholar]
  12. Cohen S., Carpenter G., King L., Jr Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity. J Biol Chem. 1980 May 25;255(10):4834–4842. [PubMed] [Google Scholar]
  13. Cohen S., Ushiro H., Stoscheck C., Chinkers M. A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles. J Biol Chem. 1982 Feb 10;257(3):1523–1531. [PubMed] [Google Scholar]
  14. Cooper J. A., Bowen-Pope D. F., Raines E., Ross R., Hunter T. Similar effects of platelet-derived growth factor and epidermal growth factor on the phosphorylation of tyrosine in cellular proteins. Cell. 1982 Nov;31(1):263–273. doi: 10.1016/0092-8674(82)90426-3. [DOI] [PubMed] [Google Scholar]
  15. Das M., Miyakawa T., Fox C. F., Pruss R. M., Aharonov A., Herschman H. R. Specific radiolabeling of a cell surface receptor for epidermal growth factor. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2790–2794. doi: 10.1073/pnas.74.7.2790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dicker P., Rozengurt E. Stimulation of DNA synthesis by tumour promoter and pure mitogenic factors. Nature. 1978 Dec 14;276(5689):723–726. doi: 10.1038/276723a0. [DOI] [PubMed] [Google Scholar]
  17. Driedger P. E., Blumberg P. M. Specific binding of phorbol ester tumor promoters. Proc Natl Acad Sci U S A. 1980 Jan;77(1):567–571. doi: 10.1073/pnas.77.1.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ek B., Westermark B., Wasteson A., Heldin C. H. Stimulation of tyrosine-specific phosphorylation by platelet-derived growth factor. Nature. 1982 Feb 4;295(5848):419–420. doi: 10.1038/295419a0. [DOI] [PubMed] [Google Scholar]
  19. Fabricant R. N., De Larco J. E., Todaro G. J. Nerve growth factor receptors on human melanoma cells in culture. Proc Natl Acad Sci U S A. 1977 Feb;74(2):565–569. doi: 10.1073/pnas.74.2.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fodge D. W., Rubin H. Activation of phosphofructokinase by stimulants of cell multiplication. Nat New Biol. 1973 Dec 12;246(154):181–183. doi: 10.1038/newbio246181a0. [DOI] [PubMed] [Google Scholar]
  21. Gajdusek C., DiCorleto P., Ross R., Schwartz S. M. An endothelial cell-derived growth factor. J Cell Biol. 1980 May;85(2):467–472. doi: 10.1083/jcb.85.2.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gates R. E., King L. E., Jr The EGF receptor-kinase has multiple phosphorylation sites. Biochem Biophys Res Commun. 1982 Mar 15;105(1):57–66. doi: 10.1016/s0006-291x(82)80010-7. [DOI] [PubMed] [Google Scholar]
  23. Glenn K., Bowen-Pope D. F., Ross R. Platelet-derived growth factor. III. Identification of a platelet-derived growth factor receptor by affinity labeling. J Biol Chem. 1982 May 10;257(9):5172–5176. [PubMed] [Google Scholar]
  24. Habenicht A. J., Glomset J. A., King W. C., Nist C., Mitchell C. D., Ross R. Early changes in phosphatidylinositol and arachidonic acid metabolism in quiescent swiss 3T3 cells stimulated to divide by platelet-derived growth factor. J Biol Chem. 1981 Dec 10;256(23):12329–12335. [PubMed] [Google Scholar]
  25. Haigler H. T., Maxfield F. R., Willingham M. C., Pastan I. Dansylcadaverine inhibits internalization of 125I-epidermal growth factor in BALB 3T3 cells. J Biol Chem. 1980 Feb 25;255(4):1239–1241. [PubMed] [Google Scholar]
  26. Haigler H. T., McKanna J. A., Cohen S. Direct visualization of the binding and internalization of a ferritin conjugate of epidermal growth factor in human carcinoma cells A-431. J Cell Biol. 1979 May;81(2):382–395. doi: 10.1083/jcb.81.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Heldin C. H., Wasteson A., Westermark B. Interaction of platelet-derived growth factor with its fibroblast receptor. Demonstration of ligand degradation and receptor modulation. J Biol Chem. 1982 Apr 25;257(8):4216–4221. [PubMed] [Google Scholar]
  28. 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]
  29. Horowitz A. D., Greenebaum E., Weinstein I. B. Identification of receptors for phorbol ester tumor promoters in intact mammalian cells and of an inhibitor of receptor binding in biologic fluids. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2315–2319. doi: 10.1073/pnas.78.4.2315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hunter T., Cooper J. A. Epidermal growth factor induces rapid tyrosine phosphorylation of proteins in A431 human tumor cells. Cell. 1981 Jun;24(3):741–752. doi: 10.1016/0092-8674(81)90100-8. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Lee L. S., Weinstein I. B. Mechanism of tumor promoter inhibition of cellular binding of epidermal growth factor. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5168–5172. doi: 10.1073/pnas.76.10.5168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lee L. S., Weinstein I. B. Tumor-promoting phorbol esters inhibit binding of epidermal growth factor to cellular receptors. Science. 1978 Oct 20;202(4365):313–315. doi: 10.1126/science.308698. [DOI] [PubMed] [Google Scholar]
  34. Magun B. E., Matrisian L. M., Bowden G. T. Epidermal growth factor. Ability of tumor promoter to alter its degradation, receptor affinity and receptor number. J Biol Chem. 1980 Jul 10;255(13):6373–6381. [PubMed] [Google Scholar]
  35. Maturo J. M., 3rd, Hollenberg M. D. Insulin receptor: interaction with nonreceptor glycoprotein from liver cell membranes. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3070–3074. doi: 10.1073/pnas.75.7.3070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Maxfield F. R., Schlessinger J., Shechter Y., Pastan I., Willingham M. C. Collection of insulin, EGF and alpha2-macroglobulin in the same patches on the surface of cultured fibroblasts and common internalization. Cell. 1978 Aug;14(4):805–810. doi: 10.1016/0092-8674(78)90336-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nishimura J., Deuel T. F. Stimulation of protein phosphorylation in Swiss mouse 3T3 cells by human platelet derived growth factor. Biochem Biophys Res Commun. 1981 Nov 16;103(1):355–361. doi: 10.1016/0006-291x(81)91700-9. [DOI] [PubMed] [Google Scholar]
  38. Owen A. J., 3rd, Geyer R. P., Antoniades H. N. Human platelet-derived growth factor stimulates amino acid transport and protein synthesis by human diploid fibroblasts in plasma-free media. Proc Natl Acad Sci U S A. 1982 May;79(10):3203–3207. doi: 10.1073/pnas.79.10.3203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. 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]
  41. Rozengurt E., Brown K. D., Pettican P. Vasopressin inhibition of epidermal growth factor binding to cultured mouse cells. J Biol Chem. 1981 Jan 25;256(2):716–722. [PubMed] [Google Scholar]
  42. Rozengurt E., Collins M., Brown K. D., Pettican P. Inhibition of epidermal growth factor binding to mouse cultured cells by fibroblast-derived growth factor. Evidence for an indirect mechanism. J Biol Chem. 1982 Apr 10;257(7):3680–3686. [PubMed] [Google Scholar]
  43. Rozengurt E., Heppel L. A. Serum rapidly stimulates ouabain-sensitive 86-RB+ influx in quiescent 3T3 cells. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4492–4495. doi: 10.1073/pnas.72.11.4492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schmidt R. A., Glomset J. A., Wight T. N., Habenicht A. J., Ross R. A study of the Influence of mevalonic acid and its metabolites on the morphology of swiss 3T3 cells. J Cell Biol. 1982 Oct;95(1):144–153. doi: 10.1083/jcb.95.1.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Shoyab M., Todaro G. J. Perturbation of membrane phospholipids alters the interaction between epidermal growth factor and its membrane receptors. Arch Biochem Biophys. 1981 Jan;206(1):222–226. doi: 10.1016/0003-9861(81)90084-9. [DOI] [PubMed] [Google Scholar]
  46. Shupnik M. A., Antoniades H. N., Tashjian A. H., Jr Platelet-derived growth factor increases prostaglandin production and decreases epidermal growth factor receptors in human osteosarcoma cells. Life Sci. 1982 Jan 25;30(4):347–353. doi: 10.1016/0024-3205(82)90571-9. [DOI] [PubMed] [Google Scholar]
  47. 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]
  48. Willingham M. C., Maxfield F. R., Pastan I. H. alpha 2 Macroglobulin binding to the plasma membrane of cultured fibroblasts. Diffuse binding followed by clustering in coated regions. J Cell Biol. 1979 Sep;82(3):614–625. doi: 10.1083/jcb.82.3.614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Witte L. D., Cornicelli J. A., Miller R. W., Goodman D. S. Effect of platelet-derived and endothelial cell-derived growth factors on the low density lipoprotein receptor pathway in cultured human fibroblasts. J Biol Chem. 1982 May 25;257(10):5392–5401. [PubMed] [Google Scholar]
  50. Wolfe R. A., Wu R., Sato G. H. Epidermal growth factor-induced down-regulation of receptor does not occur in HeLa cells grown in defined medium. Proc Natl Acad Sci U S A. 1980 May;77(5):2735–2739. doi: 10.1073/pnas.77.5.2735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Wrann M., Fox C. F., Ross R. Modulation of epidermal growth factor receptors on 3T3 cells by platelet-derived growth factor. Science. 1980 Dec 19;210(4476):1363–1365. doi: 10.1126/science.6254158. [DOI] [PubMed] [Google Scholar]
  52. de Petris S., Raff M. C. Normal distribution, patching and capping of lymphocyte surface immunoglobulin studied by electron microscopy. Nat New Biol. 1973 Feb 28;241(113):257–259. doi: 10.1038/newbio241257a0. [DOI] [PubMed] [Google Scholar]

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