Cloning and expression of human insulin-like growth factor binding protein 3.

Insulin-like growth factors (IGFs) found in plasma and other body fluids circulate in association with specific binding proteins. We report here the cloning and the nucleotide sequence of cDNAs for the growth-hormone-dependent acid-stable IGF binding protein, hIGF-BP3. The derived protein begins with a putative 27-amino acid signal peptide followed by 264 residues of the mature polypeptide. The predicted sequence contains three potential N-linked glycosylation sites and shares two region of homology with the low-molecular-weight non-growth-hormone-dependent binding proteins BP-1 and BP-2. The protein contains 18 cysteine residues clustered in the amino and carboxy termini. Chinese Hamster ovary cells transfected with this cDNA secrete a 43-45 kD protein doublet, which bound IGF. The expressed IGF-binding protein is indistinguishable from the native BP-3 found in human plasma.