The inhibitory effect of 2‐deoxyglucose on insulin receptor autophosphorylation does not depend on known serine phosphorylation sites or other conserved serine residues of the receptor β‐subunit

FEBS Letters

Stoyanov, Borislav³  Häring, Hans-U.³  Bossenmaier, Birgit²  Strack, Volker³  Lammers, Reiner³  Kellerer, Monika³  Mosthaf, Luitgard¹ 

[1] Hagedorn Research Institute, Niels Steensensvej 6, DK-2820 Gentofte, Denmark;Department of Molecular Biology, Boehringer Mannheim GmbH, Sandhofer Str. 116, D-68305 Mannheim, Germany;Eberhard-Karls-University Tübingen, Medical Clinic Department IV, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany

关键词: Insulin receptor inhibition;    2-Deoxyglucose;    Serine phosphorylation;    dIR;    Drosophila insulin receptor;    EGF;    epidermal growth factor;    FCS;    fetal calf serum;    FGF;    fibroblast growth factor;    HEK;    human embryonic kidney;    HEPES;    N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid;    hIGF-1;    human insulin like growth factor-1;    HIR;    human insulin receptor;    hIRR;    human insulin related receptor;    IDDM;    insulin dependent diabetes mellitus;    NIDDM;    non-insulin dependent diabetes mellitus;    PDGF;    platelet derived growth factor;    PMSF;    phenylmethylsulfonyl fluoride;    SDS-PAGE;    sodium dodecyl sulfate-polyacrylamide gel electrophoresis;   

DOI  :  10.1016/S0014-5793(99)00409-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Hyperglycemia induces insulin resistance in diabetic patients. It is known that supraphysiological levels of D-glucose or 2-deoxyglucose inhibit the insulin receptor and it is speculated that this effect is mediated by serine phosphorylation of the insulin receptor β-subunit and other proteins of the insulin signaling chain. To test this hypothesis we prepared point mutations of the human insulin receptor where serine was exchanged to alanine at 16 different positions, either at known phosphorylation sites or at positions which are conserved in different tyrosine kinase receptors. These receptor constructs were expressed in HEK 293 cells and the effect of 2-deoxyglucose (25 mM) on insulin (100 nM) induced receptor autophosphorylation was studied. 2-Deoxyglucose consistently inhibits insulin stimulated autophosphorylation of all constructs to the same degree as observed in wild-type human insulin receptor. The data suggest that none of the chosen serine positions are involved in 2-deoxyglucose induced receptor inhibition.

【 授权许可】

Unknown