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. 1987 Jul;84(13):4538–4542. doi: 10.1073/pnas.84.13.4538

Activity of a recombinant fusion protein between transforming growth factor type alpha and Pseudomonas toxin.

V K Chaudhary, D J FitzGerald, S Adhya, I Pastan
PMCID: PMC305125  PMID: 3299371

Abstract

The transforming growth factor type alpha gene has been fused to a modified Pseudomonas toxin gene from which the cell-recognition domain has been deleted. The chimeric gene has been expressed in Escherichia coli, and the chimeric protein, PE40-TGF-alpha, has been highly purified. PE40-TGF-alpha kills cells expressing epidermal growth factor receptors and has little activity against cells with few receptors. This chimeric protein might be useful in treating cancers that contain high numbers of epidermal growth factor 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. Allured V. S., Collier R. J., Carroll S. F., McKay D. B. Structure of exotoxin A of Pseudomonas aeruginosa at 3.0-Angstrom resolution. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1320–1324. doi: 10.1073/pnas.83.5.1320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Collier R. J., Kandel J. Structure and activity of diphtheria toxin. I. Thiol-dependent dissociation of a fraction of toxin into enzymically active and inactive fragments. J Biol Chem. 1971 Mar 10;246(5):1496–1503. [PubMed] [Google Scholar]
  3. Derynck R., Roberts A. B., Winkler M. E., Chen E. Y., Goeddel D. V. Human transforming growth factor-alpha: precursor structure and expression in E. coli. Cell. 1984 Aug;38(1):287–297. doi: 10.1016/0092-8674(84)90550-6. [DOI] [PubMed] [Google Scholar]
  4. FitzGerald D. J., Padmanabhan R., Pastan I., Willingham M. C. Adenovirus-induced release of epidermal growth factor and pseudomonas toxin into the cytosol of KB cells during receptor-mediated endocytosis. Cell. 1983 Feb;32(2):607–617. doi: 10.1016/0092-8674(83)90480-4. [DOI] [PubMed] [Google Scholar]
  5. FitzGerald D. J., Waldmann T. A., Willingham M. C., Pastan I. Pseudomonas exotoxin-anti-TAC. Cell-specific immunotoxin active against cells expressing the human T cell growth factor receptor. J Clin Invest. 1984 Sep;74(3):966–971. doi: 10.1172/JCI111516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. FitzGerald D. J., Willingham M. C., Pastan I. Antitumor effects of an immunotoxin made with Pseudomonas exotoxin in a nude mouse model of human ovarian cancer. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6627–6630. doi: 10.1073/pnas.83.17.6627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hwang J., Fitzgerald D. J., Adhya S., Pastan I. Functional domains of Pseudomonas exotoxin identified by deletion analysis of the gene expressed in E. coli. Cell. 1987 Jan 16;48(1):129–136. doi: 10.1016/0092-8674(87)90363-1. [DOI] [PubMed] [Google Scholar]
  8. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  9. Marquardt H., Hunkapiller M. W., Hood L. E., Todaro G. J. Rat transforming growth factor type 1: structure and relation to epidermal growth factor. Science. 1984 Mar 9;223(4640):1079–1082. doi: 10.1126/science.6320373. [DOI] [PubMed] [Google Scholar]
  10. Merlino G. T., Xu Y. H., Richert N., Clark A. J., Ishii S., Banks-Schlegel S., Pastan I. Elevated epidermal growth factor receptor gene copy number and expression in a squamous carcinoma cell line. J Clin Invest. 1985 Mar;75(3):1077–1079. doi: 10.1172/JCI111770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Murphy J. R., Bishai W., Borowski M., Miyanohara A., Boyd J., Nagle S. Genetic construction, expression, and melanoma-selective cytotoxicity of a diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion protein. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8258–8262. doi: 10.1073/pnas.83.21.8258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nestor J. J., Jr, Newman S. R., DeLustro B., Todaro G. J., Schreiber A. B. A synthetic fragment of rat transforming growth factor alpha with receptor binding and antigenic properties. Biochem Biophys Res Commun. 1985 May 31;129(1):226–232. doi: 10.1016/0006-291x(85)91426-3. [DOI] [PubMed] [Google Scholar]
  13. Pastan I., Willingham M. C., FitzGerald D. J. Immunotoxins. Cell. 1986 Dec 5;47(5):641–648. doi: 10.1016/0092-8674(86)90506-4. [DOI] [PubMed] [Google Scholar]
  14. Pirker R., FitzGerald D. J., Hamilton T. C., Ozols R. F., Willingham M. C., Pastan I. Anti-transferrin receptor antibody linked to Pseudomonas exotoxin as a model immunotoxin in human ovarian carcinoma cell lines. Cancer Res. 1985 Feb;45(2):751–757. [PubMed] [Google Scholar]
  15. Real F. X., Rettig W. J., Chesa P. G., Melamed M. R., Old L. J., Mendelsohn J. Expression of epidermal growth factor receptor in human cultured cells and tissues: relationship to cell lineage and stage of differentiation. Cancer Res. 1986 Sep;46(9):4726–4731. [PubMed] [Google Scholar]
  16. Reynolds F. H., Jr, Todaro G. J., Fryling C., Stephenson J. R. Human transforming growth factors induce tyrosine phosphorylation of EGF receptors. Nature. 1981 Jul 16;292(5820):259–262. doi: 10.1038/292259a0. [DOI] [PubMed] [Google Scholar]
  17. Roberts A. B., Anzano M. A., Lamb L. C., Smith J. M., Sporn M. B. New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5339–5343. doi: 10.1073/pnas.78.9.5339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Xu Y. H., Richert N., Ito S., Merlino G. T., Pastan I. Characterization of epidermal growth factor receptor gene expression in malignant and normal human cell lines. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7308–7312. doi: 10.1073/pnas.81.23.7308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. de Larco J. E., Todaro G. J. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001–4005. doi: 10.1073/pnas.75.8.4001. [DOI] [PMC free article] [PubMed] [Google Scholar]

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