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Influence of placental mannose/N-acetyl glucosamine-binding proteins on the interaction of insulin and insulin-like growth factors with their receptors

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Abstract

Placenta is a source of carbohydrate-binding proteins that function as molecular scavengers, but they could also be involved in interactions that assist in metabolic control. Mannose/N-acetyl-glucosamine (Man/GlcNAc)-binding proteins from placenta were isolated and their reactivity towards placental insulin and insulin-like growth factor receptors (IR and IGF-Rs) was analyzed. The lectins reduced the binding of insulin and IGF-I in a dose-dependent manner, while almost no effect was observed on the binding of IGF-II. The shape of the inhibition curves changed, suggesting altered binding specificity. The presence of sugar could not reverse completely the effect of the lectins, implicating both lectin-sugar and protein-protein conformational recognition. Since biological molecules in our experimental system were those that are in close relation in vivo, placental Man/GlcNAc-specific lectins may be regarded as potential allosteric modulators of lig- and-receptor interactions in a system of homologous ligands, selectively affecting only binding to tyrosine kinase type receptors (IR and IGF-1R).

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Abbreviations

CIM6P/IGF-II-R:

cation-independent mannose-6-phosphate/IGF-II receptor

Con A:

concanavalin A

GlcNAc:

N-acetyl-glucosamine

HbA1c:

glycosylated (glycated) hemoglobin

HBS:

Hepes buffered saline

IDDM:

insulin-dependent diabetes mellitus

IGF:

insulin-like growth factor

IR:

insulin receptor

IGF-1R:

type 1 IGF receptor

IGF-2R:

type 2 IGF receptor

Man:

mannose

MBL:

mannose-binding lectin

MMR:

macrophage mannose receptor

PBS:

phosphate buffered saline

WGA:

wheat germ agglutinin

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Correspondence to O. Nedić.

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Published in Russian in Biokhimiya, 2011, Vol. 76, No. 9, pp. 1230–1237.

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Nedić, O., Filimonović, D., Miković, Z. et al. Influence of placental mannose/N-acetyl glucosamine-binding proteins on the interaction of insulin and insulin-like growth factors with their receptors. Biochemistry Moscow 76, 1003–1008 (2011). https://doi.org/10.1134/S0006297911090033

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  • DOI: https://doi.org/10.1134/S0006297911090033

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