Title : Identification and molecular cloning of two new 30-kDa
insulin-like growth
factor binding
proteins isolated from adult human serum
Abstract :
- Three insulin-like growth factor binding proteins ( IGFBP ) with apparent molecular masses of 24, 28-30, and 30 kDa, nonreduced, have been isolated from human serum
- The 15 NH2-terminal amino acids of the 24-kDa binding protein are identical with those of the 30-kDa BP
- The apparent molecular mass of the latter is reduced to 24 kDa by N-glycanase, suggesting that the 30-kDa BP is the glycosylated form of the isolated 24-kDa BP
- The complete amino acid sequences derived from the cloned cDNAs represent two new IGFBPs
- They are tentatively termed IGFBP-4 and -5
- The prepeptide sequences of BP-4 and -5 contain 27 and 21, the mature proteins 213 and 237 amino acids, respectively (Mr = 22,610 and 25,980)
- The NH2- and COOH-terminal thirds of BP-4 and -5 display pronounced homology to the other three human BPs
- 16 of the 16-20 cysteines and 37 of the 213-289 amino acids (12.8-17.1%) are conserved in all five mature BPs.
- 10 amino acid positions located in the NH2-terminal region and shared by BP-1, -2, -3, and -5 are different in BP-4
- These differences may account for the preferential affinity of BP-4 for IGF II
- A most intriguing homology exists between the COOH-terminal quarter of the five IGFBPs , 10 repetitive domains of human thyroglobulin, a gastrointestinal tumor-associated antigen , and the invariant chain of the class II histocompatibility antigen
- The cDNAs of five human IGFBPs are now available
- They will allow their expression and production in sufficient quantities for in vivo studies to unravel their role in growth and metabolism