Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1, -2, -3, -4, -5 and -6).
Six different insulin-like growth factor binding proteins (IGFBPs) have been identified by molecular cloning of their cDNAs from rat and human tissues and designated as IGFBP-1, -2, -3, -4, -5 and -6. The total number of amino acid residues for the mature rat BPs ranges from 201 for IGFBP-6 to 270 for IGFBP-2, while the human homologs range from 216 for IGFBP-6 to 289 for IGFBP-2. Except for IGFBP-6, all rat and human IGFBPs contain 18 homologous cysteines; twelve are located at the N-terminal and span approximately one-third of the total amino acid sequence, while the remaining six are distributed at the C-terminal and span the last one-third of the protein sequence. Both rat and human IGFBP-4 possess two extra cysteines at the mid-region of the molecule. By contrast, rat and human IGFBP-6 contain only 14 and 16 cysteines, respectively. Absence of the two and four cysteines in the N-terminal region in the human and rat IGFBP-6 resulted in the deletion of the invariant Gly-Cys-Gly-Cys-Cys sequence which is present in all the other five IGFBPs. Both rat and human IGFBP-3 possess multiple N-linked glycosylation sites at the mid-region of the molecule, which accounts for their apparent molecular size being larger than the calculated molecular weight, based on the amino acid sequence. One potential N-linked glycosylation site is located at the mid-region of rat and human IGFBP-4, whereas only human but not rat IGFBP-6 possesses one N-linked glycosylation site at the extreme C-terminal of the molecule. An RGD sequence is found in the C-terminal of IGFBP-1 and -2. In this short review, updated information on the structural identification and molecular cloning of the six IGFBPs will be presented. In addition, the potential regulation of the BPs at the transcriptional and translational levels will be discussed.
Shimasaki
S
S
Department of Molecular Endocrinology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
Ling
N
N
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D008969:Molecular Sequence Data
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D004247:DNA