A Thermodynamic Study of Ligand Binding to the First Three Domains of the Human Insulin Receptor: Relationship between the Receptor α-Chain C-Terminal Peptide and the Site 1 Insulin Mimetic Peptides

Biochemistry ◽  
2009 ◽  
Vol 48 (23) ◽  
pp. 5492-5500 ◽  
Author(s):  
John G. Menting ◽  
Colin W. Ward ◽  
Mai B. Margetts ◽  
Michael C. Lawrence
Keyword(s):  
Ligand Binding ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Thermodynamic Study ◽  
Insulin Mimetic ◽  
Human Insulin Receptor ◽  
Mimetic Peptides ◽  
Α Chain

The ligand binding characteristics of a kinase-defective A/K1018 human insulin receptor expressed in Rat 1 fibroblasts

1990 ◽  
Vol 1053 (2-3) ◽  
pp. 185-188 ◽  
Author(s):  
Hiroshi Maegawa ◽  
Masashi Kobayashi ◽  
Katsuya Egawa ◽  
Donald A. McClain ◽  
Jerrold M. Olefsky ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Binding Characteristics ◽  
Human Insulin Receptor

scholarly journals Anti-(insulin receptor) monoclonal antibody-stimulated tyrosine phosphorylation in cells transfected with human insulin receptor cDNA

1990 ◽  
Vol 268 (3) ◽  
pp. 615-620 ◽  
Author(s):  
N P J Brindle ◽  
J M Tavare ◽  
M Dickens ◽  
J Whittaker ◽  
K Siddle
Keyword(s):  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Human Insulin ◽  
Maximum Level ◽  
Absolute Level ◽  
Insulin Receptor Tyrosine Kinase ◽  
Insulin Mimetic ◽  
Human Insulin Receptor ◽  
Receptor Cdna ◽  
Receptor Antibodies

The effects of insulin and anti-(insulin receptor) monoclonal antibodies on tyrosine phosphorylation were investigated in fibroblasts transfected with human insulin receptor cDNA (NIH 3T3HIR3.5 cells) using anti-phosphotyrosine immunoblotting. Insulin increased levels of tyrosine phosphorylation in two major proteins of molecular mass 97 kDa (pp97, assumed to be the insulin receptor beta-subunit) and 185 kDa (pp185). Insulin-mimetic anti-receptor antibodies also stimulated tyrosine phosphorylation of both pp97 and pp185. The observation of antibody-stimulated pp97 phosphorylation, as detected by immunoblotting, is in contrast with previous data which failed to show receptor autophosphorylation in NIH 3T3HIR3.5 cells labelled with [32P]P1. The effect of insulin on pp97 was maximal within 1 min, but the response to antibody was apparent only after a lag of 1-2 min and rose steadily over 20 min. The absolute level of antibody-stimulated phosphorylation of both pp97 and pp185 after 20 min was only about 20% of the maximum level induced by equivalent concentrations of insulin, even at concentrations of antibody sufficient for full occupancy of receptors. Another insulin-mimetic agent, wheat-germ agglutinin, stimulated receptor autophosphorylation with kinetics similar to those produced by the antibody. It is suggested that the relatively slow responses to both agents may be a function of the dependence on receptor cross-linking. These data are consistent with a role for the insulin receptor tyrosine kinase activity in the mechanism of action of insulin-mimetic anti-receptor antibodies.

Ligand-binding properties of the two isoforms of the human insulin receptor.

Endocrinology ◽  
1993 ◽  
Vol 132 (3) ◽  
pp. 1132-1138 ◽  
Author(s):  
Y Yamaguchi ◽  
J S Flier ◽  
H Benecke ◽  
B J Ransil ◽  
D E Moller
Keyword(s):  
Ligand Binding ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Binding Properties ◽  
Human Insulin Receptor

scholarly journals Structure‐based survey of ligand binding in the human insulin receptor

2021 ◽  
Author(s):  
Lokender Kumar ◽  
Whitney Vizgaudis ◽  
Judith Klein‐Seetharaman
Keyword(s):  
Ligand Binding ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Human Insulin Receptor

scholarly journals Structure-based survey of ligand binding in the human insulin receptor

2021 ◽  
Author(s):  
Judith Klein-Seetharaman ◽  
Whitney Vizgaudis ◽  
Lokender Kumar
Keyword(s):  
Ligand Binding ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Nutrient Balance ◽  
Docking Study ◽  
Human Insulin Receptor ◽  
Receptor Pharmacology ◽  
Entire Sequence ◽  
Treatment Of Diabetes ◽  
Structural Insights

The insulin receptor is a membrane protein responsible for regulation of nutrient balance and therefore an attractive target in the treatment of diabetes and metabolic syndrome. Pharmacology of the insulin receptor involves two distinct mechanisms, (1) activation of the receptor by insulin mimetics that bind in the extracellular domain and (2) inhibition of the receptor tyrosine kinase enzymatic activity in the cytoplasmic domain. While a complete structural picture of the full-length receptor comprising the entire sequence covering extracellular, transmembrane, juxtamembrane and cytoplasmic domains is still elusive, recent progress through cryoelectron microscopy has made it possible to describe the initial insulin ligand binding events at atomistic detail. We utilize this opportunity to obtain structural insights into the pharmacology of the insulin receptor. To this end, we conducted a comprehensive docking study of known ligands to the new structures of the receptor. Through this approach, we provide an in-depth, structure-based review of human insulin receptor pharmacology in light of the new structures.

scholarly journals Identification of a Ligand-Binding Region of the Human Insulin Receptor Encoded by the Second Exon of the Gene

1990 ◽  
Vol 4 (3) ◽  
pp. 409-416 ◽  
Author(s):  
Pierre De Meyts ◽  
Jia-Li Gu ◽  
Ronald M. Shymko ◽  
Bruce E. Kaplan ◽  
Graeme I. Bell ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Binding Region ◽  
Human Insulin Receptor
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