Regulation of the acid-labile subunit of the 150-kDa IGF-binding protein complex and its role in the circulating IGF system

Abstract

In postnatal animals, most of the IGFI and IGF-II circulates in ternary complexes of 150 kDa composed of one molecule each of IGF-I or IGF-II, IGF binding protein-3 or -5, and an acid-labile subunit (ALS). Circulation of IGF-I and IGF-II in 150-kDa complexes leads to their retention in the vascular system and promotes their endocrine actions. This review focuses on recent progress on the biology of ALS, the most important factor driving the formation of the150-kDa complex in plasma. In a variety of animals, including sheep, the single-copy ALS gene spans approximately 3.3 kb and is composed of two exons and one intron. Transcription of the ALS gene produces a mRNA of about 2.2 kb, which encodes proteins of 603 amino acids in mice and 611 amino acids in sheep. Mature ALS circulates in plasma as a glycosylated protein of 84 to 86 kDa and is organized by repeating leucine-rich domains of 24 amino acids into a donut-shaped protein. In all species studied so far, the ALS gene is expressed at high levels only in liver. In sheep, weak expression is first detected at d 130 of fetal life, increases suddenly during the 1st wk after birth, and changes little thereaf