Evaluation of interference by insulin-like growth factor I (IGF-I) binding proteins in a radioimmunoassay for IGF-I in serum from dairy cows

1991 ◽  
Vol 8 (3) ◽  
pp. 393-405 ◽  
Author(s):  
K. Plaut ◽  
W.S. Cohick ◽  
D.E. Bauman ◽  
R.C. Baxter
Keyword(s):  
Growth Factor ◽  
Dairy Cows ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I), IGF-II and des(1–3)IGF-I in rats

1991 ◽  
Vol 128 (2) ◽  
pp. 197-204 ◽  
Author(s):  
F. J. Ballard ◽  
S. E. Knowles ◽  
P. E. Walton ◽  
K. Edson ◽  
P. C. Owens ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Proteins ◽  
Rank Order ◽  
Insulin Like Growth Factor ◽  
Plasma Binding ◽  
Factor I ◽  
Igf I ◽  
The Mean ◽  
Growth Factor I ◽  
Sites Of Action

ABSTRACT Incubation of 125I-labelled insulin-like growth factor-I (IGF-I) with rat plasma at 4 °C led to the transfer of approximately half the radioactivity to 150 kDa and smaller complexes with IGF-binding proteins. The extent of association was greater with labelled IGF-II and essentially absent with the truncated IGF-I analogue, des(1–3)IGF-I. A greater degree of binding of IGF peptides with binding proteins occurred after i.v. injection of the tracers into rats, but most of the des(1–3)IGF-I radioactivity remained free. Measurement of the total plasma clearances showed the rapid removal of des(1–3)IGF-I compared with IGF-I and IGF-II; the mean clearances were 4·59, 1·20 and 1·34 ml/min per kg respectively. The mean steadystate volume of distribution was larger for des(1–3)IGF-I than for IGF-I and IGF-II (461, 167 and 181 ml/kg respectively), probably because of the differences in plasma protein binding. With all tracers, radioactivity appeared in the kidneys to a greater extent than in other organs. The amount of radioactivity found in the adrenals, brain, skin, stomach, duodenum, ileum plus jejunum and colon was in rank order, des(1–3)IGF-I > IGF-I > IGF-II. Since this ranking is the opposite of the abilities of the three IGF peptides to form complexes with plasma binding proteins, we propose that the plasma binding proteins inhibit the transfer of the growth factors to their tissue sites of action. Moreover, we suggest that IGF analogues that are cleared rapidly from blood may have greater biological potencies in vivo. Journal of Endocrinology (1991) 128, 197–204

scholarly journals Phage display-derived ligands provide structural insight into insulin-like growth factor I function

2004 ◽  
Vol 18 (2) ◽  
pp. 237-249
Author(s):  
Nicholas J. Skelton ◽  
Michelle L. Schaffer ◽  
Kurt Deshayes ◽  
Tamas Blandl ◽  
Steven Runyon ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phage Display ◽  
Binding Proteins ◽  
Cell Surface Receptor ◽  
Triple Resonance ◽  
Triple Resonance Nmr ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Insulin–like growth factor–I (IGF–I) is a central mediator of cell growth, differentiation and metabolism. Structural characterization of the protein has been hampered by a combination of internal dynamics and self–association that prevent crystallization and produce broad NMR resonances. To better characterize the functions of IGF–I, we have used phage display to identify peptides that antagonize the binding of IGF–I to its plasma binding proteins (IGFBPs) and cell–surface receptor (IGF–R). Interestingly, binding of peptide improves dramatically the quality of the NMR resonances of IGF–I, and enables the use of triple–resonance NMR methods to characterize the complexes. One such peptide, designated IGF–F1–1, has been studied in detail. In the complex, the peptide retains the same loop–helix motif seen in the free state whilst IGF–I contains three helices, as has been seen previously in low–resolution structures in the absence of ligand. The peptide binds at a hydrophobic patch between helix 1 and 3, a site identified previously by mutagenesis as a contact site for IGFBP1. Thus, antagonism of IGFBP1 binding exhibited by the peptide occurs by a simple steric occlusion mechanism. Antagonism of IGF–R binding may also be explained by a similar mechanism if receptor binding occurs by a two–site process, as has been postulated for insulin binding to its receptor. Comparisons with crystallographic structures determined for IGF–I in other complexes suggest that the region around helix 1 of IGF–I is conformationally conserved whereas the region around helix 3 adopts several different ligand–induced conformations. The ligand–induced structural variability of helix 3 appears to be a common feature across the insulin super–family. In the case of IGF–I, exchange between such conformations may be the source of the dynamic nature of free IGF–I, and likely has functional significance for the ability of IGF–I to recognize two signaling receptors and six binding proteins with high affinity.

scholarly journals Serum and tissue level of insulin-like growth factor-I (IGF-I) and IGF-I binding proteins as an index of pancreatitis and pancreatic cancer

2003 ◽  
Vol 83 (5) ◽  
pp. 239-246 ◽  
Author(s):  
Ewa Karna ◽  
Arkadiusz Surazynski ◽  
Kazimierz Orłowski ◽  
Joanna łaszkiewicz ◽  
Zbigniew Puchalski ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor ◽  
Binding Proteins ◽  
Tissue Level ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

scholarly journals Insulin-like growth factor I stimulates degradation of an mRNA transcript encoding the 14 kDa ubiquitin-conjugating enzyme

1996 ◽  
Vol 319 (2) ◽  
pp. 455-461 ◽  
Author(s):  
Simon S WING ◽  
Nathalie BEDARD
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Binding Proteins ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Mrna Transcript ◽  
Factor I ◽  
Igf I ◽  
Ubiquitin Conjugating Enzyme ◽  
Growth Factor I

Upon fasting, the ubiquitin-dependent proteolytic system is activated in skeletal muscle in parallel with the increases in rates of proteolysis. Levels of mRNA encoding the 14 kDa ubiquitin-conjugating enzyme (E214k), which can catalyse the first irreversible reaction in this pathway, rise and fall in parallel with the rates of proteolysis [Wing and Banville (1994) Am. J. Physiol. 267, E39-E48], indicating that the conjugation of ubiquitin to proteins is a regulated step. To characterize the mechanisms of this regulation, we have examined the effects of insulin, insulin-like growth factor I (IGF-I) and des(1–3) insulin-like growth factor I (DES-IGF-I), which does not bind IGF-binding proteins, on E214k mRNA levels in L6 myotubes. Insulin suppressed levels of E214k mRNA with an IC50 of 4×10-9 M, but had no effects on mRNAs encoding polyubiquitin and proteasome subunits C2 and C8, which, like E214k, also increase in skeletal muscle upon fasting. Reduction of E214k mRNA levels was more sensitive to IGF-I with an IC50 of approx. 5×10-10 M. During the incubation of these cells for 12 h there was significant secretion of IGF-I-binding proteins into the medium. DES-IGF-I, which has markedly reduced affinity for these binding proteins, was found to potently reduce E214k mRNA levels with an IC50 of 3×10-11 M. DES-IGF-I did not alter rates of transcription of the E214k gene, but enhanced the rate of degradation of the 1.2 kb mRNA transcript. The half-life of the 1.2 kb transcript was approximately one-third that of the 1.8 kb transcript and can explain the more marked regulation of this transcript observed previously. This indicates that the additional 3´ non-coding sequence in the 1.8 kb transcript confers stability. These observations suggest that IGF-I is an important regulator of E214k expression and demonstrate, for the first time, stimulation of degradation of a specific mRNA transcript by this hormone, while overall RNA accumulates.

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