Alpha-fetoprotein inhibits frog metamorphosis: implications for protein motif conservation

Abstract

Alpha-fetoprotein (AFP) is a tumor-associated fetal protein which has served as a marker for both oncogenic and ontogenetic growth. A growth regulatory segment on human AFP contains amino acid sequence identity and similarity with Rana and Xenopus albumin molecules. This study assessed the ability of both intact mammalian AFP and a derived peptide to influence thyroid induction of tail resorption during Rana catesbeiana metamorphosis. After AFP and other proteins/peptides were pre-incubated with triiodothyronine (T 3) for 1 h, they were added to intact tadpoles in 300 ml of water. Human and/or mouse AFP, at a concentration of 70 ng/ml, completely inhibited T 3-induced tail loss when measured over a 5 day period. In contrast, albumin and other proteins were without affect. A peptide (P149) with the sequence of human AFP residues #447-480 also completely blocked the tail response at a concentration of 33 ng/ml, whereas a scrambled version of this peptide was without activity. The present peptide segment derived from mammalian AFP might represent a highly conserved serum protein motif in the vertebrate phyla since it is capable of influencing growth, differentiation and transformation phenomenon in amphibians.