Epithelins 1 and 2: Isolation and Characterization of Two Cysteine-Rich Growth-Modulating Proteins

• Published in: Proceedings of the National Academy of Sciences - PNAS 1990-10, Vol.87 (20), p.7912-7916
• Main Authors: Shoyab, Mohammed, McDonald, Vicki L., Byles, Christine, Todaro, George J., Plowman, Gregory D.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cell growth; Cell Line; Cell lines; Chromatography; Chromatography, Gel; Chromatography, High Pressure Liquid; Cysteine; DNA; DNA Replication - drug effects; Epithelial cells; epithelin 1; epithelin 2; Flow velocity; Fundamental and applied biological sciences. Psychology; Granulins; growth factors; Growth Inhibitors - isolation & purification; Growth Inhibitors - pharmacology; Growth Substances - isolation & purification; Growth Substances - pharmacology; Humans; Intercellular Signaling Peptides and Proteins; Keratinocytes; Keratinocytes - cytology; Keratinocytes - drug effects; Kidney - chemistry; Kidney - physiology; Kidney cells; Kinetics; Mice; Mice, Inbred Strains; Molecular Sequence Data; Protein hormones. Growth factors. Cytokines; Proteins; Rats
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.20.7912

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 (≈ 6 kDa), acid- and heat-stable, single-chain proteins containing ≈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.