Identification and molecular cloning of two new 30-kDa insulin-like growth factor binding proteins isolated from adult human serum.
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.
Kiefer
M C
MC
Chiron Corporation, Emeryville, California 94608.
Masiarz
F R
FR
Bauer
D M
DM
Zapf
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D018975:Insulin-Like Growth Factor Binding Protein 5; D009841:Oligonucleotides; D013002:Somatomedins; D004247:DNA