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.