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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Oct;87(20):7912–7916. doi: 10.1073/pnas.87.20.7912

Epithelins 1 and 2: isolation and characterization of two cysteine-rich growth-modulating proteins.

M Shoyab 1, V L McDonald 1, C Byles 1, G J Todaro 1, G D Plowman 1
PMCID: PMC54861  PMID: 2236009

Abstract

Two proteins, termed epithelin 1 and epithelin 2, that inhibit the growth of A431 cells, derived from a human epidermal carcinoma of the vulva, have been purified from rat kidney. Epithelin 1 stimulates the proliferation of murine keratinocytes, whereas epithelin 2 inhibits the epithelin 1-elicited growth of these cells. Thus epithelin 1 and 2 behave as agonist and antagonist, respectively, for normal epithelial cells. Epithelins are low molecular mass (approximately 6 kDa), acid- and heat-stable, single-chain proteins containing approximately 20% cysteine. Some of these cysteines form disulfide linkage(s) that are essential for biological activity. The amino-terminal amino acid sequences of epithelin 1 and epithelin 2 have been determined. The two proteins showed no substantial sequence homology with other proteins. However, a significant homology was seen between the amino-terminal sequences of epithelin 1 and epithelin 2. Epithelins 1 and 2, therefore, appear to represent members of a distinct family of growth regulators.

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Selected References

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  1. Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beutler B., Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987 Feb 12;316(7):379–385. doi: 10.1056/NEJM198702123160705. [DOI] [PubMed] [Google Scholar]
  3. Carpenter G., Zendegui J. A biological assay for epidermal growth factor/urogastrone and related polypeptides. Anal Biochem. 1986 Mar;153(2):279–282. doi: 10.1016/0003-2697(86)90093-x. [DOI] [PubMed] [Google Scholar]
  4. Clemens M. J., McNurlan M. A. Regulation of cell proliferation and differentiation by interferons. Biochem J. 1985 Mar 1;226(2):345–360. doi: 10.1042/bj2260345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fryling C. M., Iwata K. K., Johnson P. A., Knott W. B., Todaro G. J. Two distinct tumor cell growth-inhibiting factors from a human rhabdomyosarcoma cell line. Cancer Res. 1985 Jun;45(6):2695–2699. [PubMed] [Google Scholar]
  6. Goustin A. S., Leof E. B., Shipley G. D., Moses H. L. Growth factors and cancer. Cancer Res. 1986 Mar;46(3):1015–1029. [PubMed] [Google Scholar]
  7. Iwata K. K., Fryling C. M., Knott W. B., Todaro G. J. Isolation of tumor cell growth-inhibiting factors from a human rhabdomyosarcoma cell line. Cancer Res. 1985 Jun;45(6):2689–2694. [PubMed] [Google Scholar]
  8. Melchers F., Andersson J. B cell activation: three steps and their variations. Cell. 1984 Jul;37(3):713–720. doi: 10.1016/0092-8674(84)90407-0. [DOI] [PubMed] [Google Scholar]
  9. Nathan C. F. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Old L. J. Tumour necrosis factor. Polypeptide mediator network. 1987 Mar 26-Apr 1Nature. 326(6111):330–331. doi: 10.1038/326330a0. [DOI] [PubMed] [Google Scholar]
  11. Pardee A. B. Molecules involved in proliferation of normal and cancer cells: presidential address. Cancer Res. 1987 Mar 15;47(6):1488–1491. [PubMed] [Google Scholar]
  12. Rozengurt E. Early signals in the mitogenic response. Science. 1986 Oct 10;234(4773):161–166. doi: 10.1126/science.3018928. [DOI] [PubMed] [Google Scholar]
  13. Sachs L. Growth, differentiation and the reversal of malignancy. Sci Am. 1986 Jan;254(1):40–47. doi: 10.1038/scientificamerican0186-40. [DOI] [PubMed] [Google Scholar]
  14. Schägger H., von Jagow G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem. 1987 Nov 1;166(2):368–379. doi: 10.1016/0003-2697(87)90587-2. [DOI] [PubMed] [Google Scholar]
  15. Shoyab M., McDonald V. L., Bradley J. G., Todaro G. J. Amphiregulin: a bifunctional growth-modulating glycoprotein produced by the phorbol 12-myristate 13-acetate-treated human breast adenocarcinoma cell line MCF-7. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6528–6532. doi: 10.1073/pnas.85.17.6528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shoyab M., Plowman G. D., McDonald V. L., Bradley J. G., Todaro G. J. Structure and function of human amphiregulin: a member of the epidermal growth factor family. Science. 1989 Feb 24;243(4894 Pt 1):1074–1076. doi: 10.1126/science.2466334. [DOI] [PubMed] [Google Scholar]
  17. Sporn M. B., Roberts A. B. Peptide growth factors and inflammation, tissue repair, and cancer. J Clin Invest. 1986 Aug;78(2):329–332. doi: 10.1172/JCI112580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sporn M. B., Todaro G. J. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980 Oct 9;303(15):878–880. doi: 10.1056/NEJM198010093031511. [DOI] [PubMed] [Google Scholar]
  19. Weissman B. E., Aaronson S. A. BALB and Kirsten murine sarcoma viruses alter growth and differentiation of EGF-dependent balb/c mouse epidermal keratinocyte lines. Cell. 1983 Feb;32(2):599–606. doi: 10.1016/0092-8674(83)90479-8. [DOI] [PubMed] [Google Scholar]
  20. Wolpe S. D., Cerami A. Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines. FASEB J. 1989 Dec;3(14):2565–2573. doi: 10.1096/fasebj.3.14.2687068. [DOI] [PubMed] [Google Scholar]
  21. Wray W., Boulikas T., Wray V. P., Hancock R. Silver staining of proteins in polyacrylamide gels. Anal Biochem. 1981 Nov 15;118(1):197–203. doi: 10.1016/0003-2697(81)90179-2. [DOI] [PubMed] [Google Scholar]
  22. Zarling J. M., Shoyab M., Marquardt H., Hanson M. B., Lioubin M. N., Todaro G. J. Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9739–9743. doi: 10.1073/pnas.83.24.9739. [DOI] [PMC free article] [PubMed] [Google Scholar]

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