Skip to main content
NCBI home page
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.

Full text

PDF
7912

Images in this article

7915Image
on p.7915

Selected References

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

  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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES