A comparison of the biological activity of the recombinant intact and truncated insulin-like growth factor 1 (IGF-1).
A truncated form of insulin-like growth factor 1 (IGF-1), which lacked the aminoterminal tripeptide Gly-Pro-Glu has been isolated from human fetal and adult brain. This truncated IGF-1 displayed more potent cross-reactivity and biological action on brain cells than IGF-1 isolated from human serum. We now present data on a recombinant DNA-derived truncated IGF-1 lacking the aminoterminal tripeptide. Recombinant truncated IGF-1 was 1.4-5-times more potent than recombinant and natural IGF-1 in displacing [125 I]IGF-1 from human fetal and adult brain and placenta membranes. These differences were slightly enhanced when truncated IGF-1 was used as radioligand. The relative potencies compared to insulin-like growth factor 2 (IGF-2) in displacing [125I]IGF-2 from rat liver membranes were recombinant truncated IGF-1, 0.3% and recombinant IGF-1, 0.2%. Recombinant truncated IGF-1 displayed 100-fold reduced affinity for the low molecular weight binding protein (IGF-BP) isolated from human amniotic fluid when compared to recombinant IGF-1. Likewise, the IGF-BP was 100-fold less potent in inhibiting the receptor binding of recombinant truncated IGF-1 than that of recombinant IGF-1. Recombinant truncated IGF-1 was 4-times more potent than recombinant and natural IGF-1 in stimulating DNA synthesis in fetal rat brain cells. This biological activity of recombinant truncated IGF-1 was not affected by the IGF-BP at concentrations which abolished the biological activity of recombinant IGF-1. The hypothesis that IGF-BP bound intact IGF-1 represents the endocrine form of IGF-1, whereas truncated IGF-1 represents the paracrine or autocrine form of IGF-1, is proposed.
Carlsson-Skwirut
C
C
Karolinska Institute's Department of Pathology, Karolinska Hospital, Stockholm, Sweden.
Lake
M
M
Hartmanis
M
M
Hall
K
K
Sara
V R
VR
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism; D003429:Cross Reactions; D006801:Humans; D066298:In Vitro Techniques; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II