Molecular Endocrinology, Vol 6, 870-876, Copyright © 1992 by Endocrine Society

ARTICLES

Structure and functional expression of the acid-labile subunit of the insulin-like growth factor-binding protein complex

SR Leong, RC Baxter, T Camerato, J Dai and WI Wood
Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080.

Nearly all of the insulin-like growth factor (IGF) in the circulation is bound in a heterotrimeric complex composed of IGF, IGF-binding protein-3, and the acid-labile subunit (ALS). Full-length clones encoding ALS have been isolated from human liver cDNA libraries by using probes based on amino acid sequence data from the purified protein. These clones encode a mature protein of 578 amino acids preceded by a 27-amino acid hydrophobic sequence indicative of a secretion signal. Expression of the cDNA clones in mammalian tissue culture cells results in the secretion into the culture medium of ALS activity that can form the expected complex with IGF-I and IGF-binding protein-3. The amino acid sequence of ALS is largely composed of 18-20 leucine-rich repeats of 24 amino acids. These repeats are found in a number of diverse proteins that, like ALS, participate in protein- protein interactions.

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