In vivo processed fragments of IGF binding protein-2 copurified with bioactive IGF-II.
Proteolysis of insulin-like growth factor binding proteins (IGFBPs), the major carrier of insulin-like growth factors (IGFs) in the circulation, is an essential mechanism to regulate the bioavailability and half-live of IGFs. Screening for peptides in human hemofiltrate, stimulating the survival of PC-12 cells, resulted in the isolation of C-terminal IGFBP-2 fragments and intact IGF-II co-eluting during the chromatographic purification procedure. The IGFBP-2 fragments exhibited molecular masses of 12.7 and 12.9kDa and started with Gly169 and Gly167, respectively. The fragments were able to bind both IGFs. The stimulatory effect of the purified fraction on the survival of the PC-12 cells could be assigned exclusively to IGF-II, since it was abolished by the addition of neutralizing IGF-II antibodies. We suggest that in the circulation IGF-II is not only complexed with intact IGFBP but also with processed IGFBP-2 fragments not impairing the biological activity of IGF-II.
Ständker
Ludger
L
IPF PharmaCeuticals GmbH(IPF), Feodor Lynen Strasse 31, Hannover D-30625, Germany. L.staendker@ipf-pharmaceuticals.de
Kübler
Bernd
B
Obendorf
Maik
M
Braulke
Thomas
T
Forssmann
Wolf-Georg
WG
Mark
Silke
S
D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000302:isolation & purification* / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D016415:Sequence Alignment
D018971:Insulin-Like Growth Factor Binding Protein 2; D010446:Peptide Fragments; D007335:Insulin-Like Growth Factor II