Isolation from adult human serum of four insulin-like growth factor (IGF) binding proteins and molecular cloning of one of them that is increased by IGF I administration and in extrapancreatic tumor hypoglycemia.

Abstract

We have isolated four insulin-like growth factor binding proteins (IGFBPs) from adult human serum by insulin-like growth factor (IGF) I affinity chromatography and high performance liquid chromatography. A 36-kDa binding protein (BP), not digestible with N-glycanase, is increased in patients with extrapancreatic tumor hypoglycemia and during IGF I administration in healthy adults. Its 38 NH2-terminal amino acids are identical to those of an IGFBP sequence derived from a human cDNA that cross-hybridizes with the rat IGFBP-2 cDNA. With probes encoding a NH2-terminal, COOH-terminal, and a middle region of this protein we have obtained three cDNA clones from a Hep G2 cDNA library; one encodes human IGFBP-2, and the other two presumably represent unspliced heteronuclear and alternatively spliced mRNA, respectively. A 28-30-kDa IGFBP represents a novel BP species in human serum. Its 30 NH2-terminal amino acids are not homologous to IGFBP-1, -2, or -3. It is not digestible with N-glycanase and does not bind 125I-IGF I. The NH2-terminal sequences of a 42/45- and a 31-kDa IGFBP are identical to that of human IGFBP-3. The 42/45-kDa proteins are two glycosylation variants of BP-3. The 31-kDa protein presumably is a degradation product of BP-3 that lacks the COOH terminus. It is likely that the different IGFBPs modulate auto-/paracrine and endocrine effects of IGFs on growth and metabolism in a different and specific manner.

• Authors: J Zapf, M Kiefer, J Merryweather, F Musiarz, D Bauer, W Born, J A Fischer, E R Froesch
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 265 Issue 25 Pg. 14892-8 (Sep 05 1990) ISSN: 0021-9258 [Print] United States
• PMID: 1697583 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Insulin-Like Growth Factor Binding Proteins
• Ligands
• Oligonucleotide Probes
• RNA, Messenger
• Somatomedins
• Insulin-Like Growth Factor I

Topics

• Adult
• Amino Acid Sequence
• Animals
• Base Sequence
• Carcinoma, Hepatocellular
• Carrier Proteins (genetics, isolation & purification, metabolism)
• Cell Line
• Chromatography, Affinity
• Cloning, Molecular
• Gene Library
• Humans
• Hypoglycemia (blood)
• Insulin-Like Growth Factor Binding Proteins
• Insulin-Like Growth Factor I (metabolism, pharmacology)
• Ligands
• Liver Neoplasms
• Molecular Sequence Data
• Neoplasms (blood, physiopathology)
• Oligonucleotide Probes
• Plasmids
• RNA, Messenger (genetics, isolation & purification)
• Reference Values
• Sequence Homology, Nucleic Acid
• Somatomedins (pharmacology)