Structural analysis of the interaction of IGF I with the IGF types 1 and 2 and insulin receptors

Conference · Fri May 01 00:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6075179

Cascieri, M A; Chicchi, G G; Hayes, N S; Green, B G; Applebaum, J A; Bayne, M L

A synthetic gene for human IGF I has been synthesized which directs the synthesis and secretion of fully active human IGF I (rIGF I) from yeast. rIGF I inhibits binding of /sup 125/I-IGF I to type 1 IGF receptors from human placenta (IGF-R1, IC50 = 4 nM), binding of /sup 125/I-insulin to insulin receptors (IR, IC50 = 881 nM), binding of /sup 125/I-MSA to type 2 IGF receptors from rat liver (IGF-R2, IC50 = 80 nM), and binding of /sup 125/I-IGF I to crude human serum binding protein (hBP, IC50 = 0.42 nM). rIGF I is equipotent to human IGF I in stimulating glucose transport in murine BC3H1 cells and in stimulating DNA synthesis in rat A10 cells. Site directed mutagenesis of the synthetic gene is being used to characterize the structural requirements for binding to these receptors. IGF I (FFY) B(23-25) is equipotent to rIGF I at the IGF-R1 (6.9 nM), the IGF-R2 (36 nM), and the IR (841 nM) and is less potent at the hBP (1.7 nM). In contrast, IGF I(SFY) B(23-25) is 20-fold less potent than rIGF I at the IGF-R1 and is 10-fold less potent than rIGF I at hBP. This peptide is greater than 10-fold less active at the IGF-R2 and the IR. This peptide is a full agonist in the cell assays but 20-50 fold less potent than rIGF I. These data are consistent with the hypothesis that the F to S change destabilizes the tertiary structure of IGF I.

• Research Organization: Merck Sharp and Dohme Research Lab., Rahway, NJ
• OSTI ID: 6075179
• Report Number(s): CONF-870644-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
INSULIN
BIOCHEMICAL REACTION KINETICS
RECEPTORS
PEPTIDE HORMONES
MOLECULAR STRUCTURE
GENES
IODINE 125
LIVER
MAN
RATS
TRACER TECHNIQUES
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PRIMATES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques