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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
Author(s) -
Strack Volker,
Bossenmaier Birgit,
Stoyanov Borislav,
Mosthaf Luitgard,
Kellerer Monika,
Lammers Reiner,
Häring Hans-U.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00409-3
Subject(s) - autophosphorylation , serine , phosphorylation , insulin receptor , protein subunit , chemistry , inhibitory postsynaptic potential , biochemistry , interleukin 10 receptor, alpha subunit , microbiology and biotechnology , insulin , biology , g alpha subunit , endocrinology , insulin resistance , protein kinase a , gene
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.