STRUCTURAL CHARACTERISATION OF SUBSTRATE BINDING TO THE HUMAN INSULIN RECEPTOR TYROSINE KINASE DOMAIN

1992 ◽  
Vol 20 (3) ◽  
pp. 269S-269S ◽  
Author(s):  
Yuan Gao ◽  
Noeleen Keane ◽  
Barry A. Levine ◽  
Riki Alejos ◽  
Leland Ellis
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Receptor Tyrosine Kinase ◽  
Substrate Binding ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Insulin Receptor Tyrosine Kinase ◽  
Structural Characterisation ◽  
Human Insulin Receptor

scholarly journals Antibodies to insulin receptor tyrosine kinase stimulate its activity towards exogenous substrates without inducing receptor autophosphorylation

1989 ◽  
Vol 260 (3) ◽  
pp. 749-756 ◽  
Author(s):  
V Baron ◽  
N Gautier ◽  
N Rochet ◽  
R Ballotti ◽  
B Rossi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Receptor Tyrosine Kinase ◽  
Kinase Activity ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Insulin Receptor Tyrosine Kinase ◽  
Substrate Phosphorylation ◽  
Exogenous Substrates

Anti-peptide antibodies directed against a highly-conserved sequence of the insulin receptor tyrosine kinase domain have been used to study the relationship between this specific region and kinase activation. Antibodies have been prepared by the injection into a rabbit of a synthetic peptide (P2) corresponding to residues 1110-1125 of the proreceptor. The peptide exhibits 88-95% sequence similarity with the corresponding sequence in the v-ros protein and in receptors for epidermal growth factor and for insulin-like growth factor 1. Two antibodies with different specificities could be separated from total antiserum obtained after immunization with P2. One antibody [anti-(P-Tyr)] cross-reacted with phosphotyrosine and immunoprecipitated solely autophosphorylated receptors. This antibody was shown to increase or decrease the receptor tyrosine kinase activity depending on its concentration. In all circumstances receptor autophosphorylation and substrate phosphorylation were modulated in a parallel fashion. The second antibody (anti-P2) failed to immunoprecipitate the insulin receptor, but was found to interact with both the peptide and the receptor by e.l.i.s.a. assay. Using a tyrosine co-polymer we found that anti-P2 activated the insulin receptor kinase leading to substrate phosphorylation at a level similar to that observed with insulin. This effect was additive to the hormonal effect. In contrast, receptor autophosphorylation was not modified by the anti-peptide. The differential effect of this anti-peptide further supports the idea that receptor autophosphorylation and kinase activity towards exogenous substrates might be independently regulated. Finally, our data suggest that conformational changes in the receptor tyrosine kinase domain may be sufficient for activation of its enzymic activity.

N.m.r. structural studies on the tyrosine kinase domain of the human insulin receptor

1989 ◽  
Vol 17 (5) ◽  
pp. 899-899
Author(s):  
ROBERT A. ATKINSON ◽  
WAYNE J. FAIRBROTHER ◽  
BARRY A. LEVINE ◽  
JEREMY TAVARÈ ◽  
BEA CLACK ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Structural Studies ◽  
Human Insulin Receptor

Substrate specificity of the insulin receptor tyrosine kinase domain

1993 ◽  
Vol 21 (3) ◽  
pp. 266S-266S
Author(s):  
Noeleen E. Keane ◽  
Barry A. Levine ◽  
Philip Quirk ◽  
Bernard Calas ◽  
Alain Chavanieu ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Receptor Tyrosine Kinase ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Insulin Receptor Tyrosine Kinase

scholarly journals Insulin Resistance Induced by Hyperinsulinemia Coincides with a Persistent Alteration at the Insulin Receptor Tyrosine Kinase Domain

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e108693 ◽  
Author(s):  
Karyn J. Catalano ◽  
Betty A. Maddux ◽  
Jaroslaw Szary ◽  
Jack F. Youngren ◽  
Ira D. Goldfine ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Receptor Tyrosine Kinase ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Insulin Receptor Tyrosine Kinase

Insulin receptor tyrosine kinase domain auto-dephosphorylation

1992 ◽  
Vol 189 (3) ◽  
pp. 1457-1463 ◽  
Author(s):  
Philip A. Gruppuso ◽  
Joan M. Boylan ◽  
Barry A. Levine ◽  
Leland Ellis
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Receptor Tyrosine Kinase ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Insulin Receptor Tyrosine Kinase

Crystal structure of the tyrosine kinase domain of the human insulin receptor

Nature ◽  
1994 ◽  
Vol 372 (6508) ◽  
pp. 746-754 ◽  
Author(s):  
Stevan R. Hubbard ◽  
Lei Wei ◽  
Wayne A. Hendrickson
Keyword(s):  
Crystal Structure ◽  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Human Insulin Receptor
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