title: A 30-kDa fragment of insulin-like growth factor (IGF) binding protein-3 in human pregnancy serum with strongly reduced IGF-I binding.
abstract: Proteolytic cleavage of insulin-like growth factor (IGF) binding protein (IGFBP)-3 during pregnancy is likely to have both IGF-dependent and -independent effects on maternal, placental and fetal growth and metabolism. A 30-kDa proteolytic IGFBP-3 fragment was isolated from third trimester pregnancy human serum and identified by N- and C-terminal amino acid sequence analysis and mass spectrometry to correspond to residues 1-212 of the parent protein. This fragment is the dominating IGFBP-3 immunoreactive species in pregnancy serum. The 30-kDa fragment was also detected in serum of non-pregnant women where it coexists with intact IGFBP-3. Using biosensor technology, (1-212)IGFBP-3 was found to have 11-fold lower affinity for IGF-I compared to intact IGFBP-3, while a 4-fold decrease in affinity was found for IGF-II. Tests with des(1-3)IGF-I suggest fast binding of IGF-I to the N-terminal region of IGFBP-3 and similar affinity to a slow binding site in the C-terminal region.
authors.affiliation: Department of Woman and Child Health, Pediatric Endocrinology Unit (Q2:08), Astrid Lindgren Children's Hospital, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Ahlsén
authors.forename: C
authors.initials: C
authors.lastname: Carlsson-Skwirut
authors.forename: A P
authors.initials: AP
authors.lastname: Jonsson
authors.forename: E
authors.initials: E
authors.lastname: Cederlund
authors.forename: T
authors.initials: T
authors.lastname: Bergman
authors.forename: P
authors.initials: P
authors.lastname: Bang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D011247:Pregnancy / Q000097:blood*; D020539:Sequence Analysis, Protein
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D010446:Peptide Fragments; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II