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. 1986 Aug;5(8):1809–1814. doi: 10.1002/j.1460-2075.1986.tb04430.x

The role of EGF receptor transmodulation in embryonal carcinoma-derived growth factor-induced mitogenesis.

J K Heath, L Mahadevan, J G Foulkes
PMCID: PMC1167044  PMID: 3489616

Abstract

Exposure of quiescent 10T1/2 fibroblast cells to embryonal carcinoma-derived growth factor (ECDGF) results in a rapid temperature and ECDGF concentration-dependent inhibition of [125I]EGF binding to the epidermal growth factor (EGF) receptor (transmodulation). ECDGF predominantly inhibits the association of [125I]EGF with a high affinity subclass of EGF receptors, and induces increased phosphorylation of the EGF receptor on serine and threonine residues. No mitogenic effect of EGF can be detected in the presence of ECDGF concentrations which induce maximal EGF receptor transmodulation. ECDGF-induced EGF receptor transmodulation is sensitive to phorbol ester-induced desensitization whereas ECDGF-induced DNA synthesis is unaffected by prolonged pre-treatment with biologically active phorbol ester. These findings suggest that EGF receptor transmodulation is not essential for ECDGF mitogenicity but may inhibit EGF-induced DNA synthesis.

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Selected References

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

  1. Blackshear P. J., Witters L. A., Girard P. R., Kuo J. F., Quamo S. N. Growth factor-stimulated protein phosphorylation in 3T3-L1 cells. Evidence for protein kinase C-dependent and -independent pathways. J Biol Chem. 1985 Oct 25;260(24):13304–13315. [PubMed] [Google Scholar]
  2. Bowen-Pope D. F., Dicorleto P. E., Ross R. Interactions between the receptors for platelet-derived growth factor and epidermal growth factor. J Cell Biol. 1983 Mar;96(3):679–683. doi: 10.1083/jcb.96.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown K. D., Blay J., Irvine R. F., Heslop J. P., Berridge M. J. Reduction of epidermal growth factor receptor affinity by heterologous ligands: evidence for a mechanism involving the breakdown of phosphoinositides and the activation of protein kinase C. Biochem Biophys Res Commun. 1984 Aug 30;123(1):377–384. doi: 10.1016/0006-291x(84)90424-8. [DOI] [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. Cochet C., Gill G. N., Meisenhelder J., Cooper J. A., Hunter T. C-kinase phosphorylates the epidermal growth factor receptor and reduces its epidermal growth factor-stimulated tyrosine protein kinase activity. J Biol Chem. 1984 Feb 25;259(4):2553–2558. [PubMed] [Google Scholar]
  6. Collins M. K., Rozengurt E. Homologous and heterologous mitogenic desensitization of Swiss 3T3 cells to phorbol esters and vasopressin: role of receptor and postreceptor steps. J Cell Physiol. 1984 Feb;118(2):133–142. doi: 10.1002/jcp.1041180205. [DOI] [PubMed] [Google Scholar]
  7. Collins M. K., Sinnett-Smith J. W., Rozengurt E. Platelet-derived growth factor treatment decreases the affinity of the epidermal growth factor receptors of Swiss 3T3 cells. J Biol Chem. 1983 Oct 10;258(19):11689–11693. [PubMed] [Google Scholar]
  8. Corvera S., Schwarz K. R., Graham R. M., García-Sáinz J. A. Phorbol esters inhibit alpha 1-adrenergic effects and decrease the affinity of liver cell alpha 1-adrenergic receptors for (-)-epinephrine. J Biol Chem. 1986 Jan 15;261(2):520–526. [PubMed] [Google Scholar]
  9. Coughlin S. R., Lee W. M., Williams P. W., Giels G. M., Williams L. T. c-myc gene expression is stimulated by agents that activate protein kinase C and does not account for the mitogenic effect of PDGF. Cell. 1985 Nov;43(1):243–251. doi: 10.1016/0092-8674(85)90029-7. [DOI] [PubMed] [Google Scholar]
  10. Davis R. J., Czech M. P. Platelet-derived growth factor mimics phorbol diester action on epidermal growth factor receptor phosphorylation at threonine-654. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4080–4084. doi: 10.1073/pnas.82.12.4080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Davis R. J., Czech M. P. Tumor-promoting phorbol diesters cause the phosphorylation of epidermal growth factor receptors in normal human fibroblasts at threonine-654. Proc Natl Acad Sci U S A. 1985 Apr;82(7):1974–1978. doi: 10.1073/pnas.82.7.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Friedman B., Frackelton A. R., Jr, Ross A. H., Connors J. M., Fujiki H., Sugimura T., Rosner M. R. Tumor promoters block tyrosine-specific phosphorylation of the epidermal growth factor receptor. Proc Natl Acad Sci U S A. 1984 May;81(10):3034–3038. doi: 10.1073/pnas.81.10.3034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heath J. K., Isacke C. M. PC13 embryonal carcinoma-derived growth factor. EMBO J. 1984 Dec 1;3(12):2957–2962. doi: 10.1002/j.1460-2075.1984.tb02240.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heath J. K., Rees A. R. Growth factors in mammalian embryogenesis. Ciba Found Symp. 1985;116:3–22. doi: 10.1002/9780470720974.ch2. [DOI] [PubMed] [Google Scholar]
  15. Hunter T., Ling N., Cooper J. A. Protein kinase C phosphorylation of the EGF receptor at a threonine residue close to the cytoplasmic face of the plasma membrane. Nature. 1984 Oct 4;311(5985):480–483. doi: 10.1038/311480a0. [DOI] [PubMed] [Google Scholar]
  16. Hunter T., Sefton B. M. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311–1315. doi: 10.1073/pnas.77.3.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Iwashita S., Fox C. F. Epidermal growth factor and potent phorbol tumor promoters induce epidermal growth factor receptor phosphorylation in a similar but distinctively different manner in human epidermoid carcinoma A431 cells. J Biol Chem. 1984 Feb 25;259(4):2559–2567. [PubMed] [Google Scholar]
  18. King A. C., Cuatrecasas P. Resolution of high and low affinity epidermal growth factor receptors. Inhibition of high affinity component by low temperature, cycloheximide, and phorbol esters. J Biol Chem. 1982 Mar 25;257(6):3053–3060. [PubMed] [Google Scholar]
  19. 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]
  20. McCaffrey P. G., Friedman B., Rosner M. R. Diacylglycerol modulates binding and phosphorylation of the epidermal growth factor receptor. J Biol Chem. 1984 Oct 25;259(20):12502–12507. [PubMed] [Google Scholar]
  21. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  22. Rodriguez-Pena A., Rozengurt E. Disappearance of Ca2+-sensitive, phospholipid-dependent protein kinase activity in phorbol ester-treated 3T3 cells. Biochem Biophys Res Commun. 1984 May 16;120(3):1053–1059. doi: 10.1016/s0006-291x(84)80213-2. [DOI] [PubMed] [Google Scholar]
  23. Rozengurt E., Collins M. Molecular aspects of growth factor action: receptors and intracellular signals. J Pathol. 1983 Nov;141(3):309–331. doi: 10.1002/path.1711410310. [DOI] [PubMed] [Google Scholar]
  24. Savage C. R., Jr, Cohen S. Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization. J Biol Chem. 1972 Dec 10;247(23):7609–7611. [PubMed] [Google Scholar]
  25. Shoyab M., De Larco J. E., Todaro G. J. Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptors. Nature. 1979 May 31;279(5712):387–391. doi: 10.1038/279387a0. [DOI] [PubMed] [Google Scholar]
  26. Sinnett-Smith J. W., Rozengurt E. Diacylglycerol treatment rapidly decreases the affinity of the epidermal growth factor receptors of Swiss 3T3 cells. J Cell Physiol. 1985 Jul;124(1):81–86. doi: 10.1002/jcp.1041240114. [DOI] [PubMed] [Google Scholar]
  27. Takayama S., White M. F., Lauris V., Kahn C. R. Phorbol esters modulate insulin receptor phosphorylation and insulin action in cultured hepatoma cells. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7797–7801. doi: 10.1073/pnas.81.24.7797. [DOI] [PMC free article] [PubMed] [Google Scholar]

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