Baculoviral Expression of a Natural Inhibitor of the Human Insulin Receptor Tyrosine Kinase

1995 ◽  
Vol 208 (2) ◽  
pp. 879-885 ◽  
Author(s):  
P.R. Srinivas ◽  
A.S. Goustin ◽  
G. Grunberger
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Receptor Tyrosine Kinase ◽  
Insulin Receptor Tyrosine Kinase ◽  
Human Insulin Receptor ◽  
Natural Inhibitor

scholarly journals Functional characterization of the promoter of pp63, a gene encoding a natural inhibitor of the insulin receptor tyrosine kinase

1992 ◽  
Vol 20 (8) ◽  
pp. 1983-1990 ◽  
Author(s):  
Laurence Falquerho ◽  
Laurent Paquereau ◽  
Marie José Vilarem ◽  
Simon Galas ◽  
Gilles Patey ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Receptor Tyrosine Kinase ◽  
Functional Characterization ◽  
Gene Encoding ◽  
Insulin Receptor Tyrosine Kinase ◽  
Natural Inhibitor

scholarly journals Site-specific dephosphorylation and deactivation of the human insulin receptor tyrosine kinase by particulate and soluble phosphotyrosyl protein phosphatases

1991 ◽  
Vol 275 (2) ◽  
pp. 413-418 ◽  
Author(s):  
M J King ◽  
R P Sharma ◽  
G J Sale
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Receptor Tyrosine Kinase ◽  
Protein Phosphatases ◽  
Insulin Receptors ◽  
Membrane Domains ◽  
Insulin Receptor Tyrosine Kinase ◽  
Kinase Activation ◽  
Human Insulin Receptor ◽  
Highly Sensitive

Insulin receptor tyrosine kinase activation, induced by insulin-stimulated autophosphorylation, was measured using a synthetic peptide containing residues 1142-1153 of the insulin receptor and shown to be reversed by both particulate and soluble phosphotyrosyl protein phosphatases from rat liver. Deactivation of the tyrosine kinase was highly sensitive to phosphatase action and was correlated best with disappearance of insulin receptors triphosphorylated in the tyrosine-1150 domain. Dephosphorylation of the di- and mono-phosphorylated forms of the tyrosine-1150 domain generated during dephosphorylation or of phosphorylation sites in the C-terminal or putative juxta-membrane domains occurred 3- greater than 10-fold more slowly than deactivation of the tyrosine kinase, and these phosphorylated species did not appear to appreciably (less than 20%) contribute to tyrosine kinase activation. These results indicate that the transition from the triply to the doubly phosphorylated form of the tyrosine-1150 domain acts as an important switch for deactivation of the insulin receptor tyrosine kinase during dephosphorylation. The exquisite sensitivity of this dephosphorylation/deactivation event to phosphotyrosyl protein phosphatase action, combined with the high affinities of this phosphatases for substrates and the high activities of the phosphatases in cells, suggests that the tyrosine kinase activity expressed by insulin-stimulated insulin receptors is likely to be stringently regulated.

scholarly journals Sustained signalling from the insulin receptor after stimulation with insulin analogues exhibiting increased mitogenic potency

1996 ◽  
Vol 315 (1) ◽  
pp. 271-279 ◽  
Author(s):  
Bo Falck HANSEN ◽  
Gillian M. DANIELSEN ◽  
Kirsten DREJER ◽  
Anders R. SØRENSEN ◽  
Finn C. WIBERG ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Receptor Tyrosine Kinase ◽  
Half Life ◽  
Insulin Analogues ◽  
Metabolic Potential ◽  
Insulin Receptor Tyrosine Kinase ◽  
Potency Ratio ◽  
Sustained Activation

The metabolic and mitogenic potencies of six different insulin analogues were determined by measuring glucose transport in primary adipocytes and DNA synthesis in CHO cells respectively. Three analogues showed a disproportionately high mitogenic potency compared with their metabolic potency, and were up to 7 times more mitogenically than metabolically potent when compared with human insulin. The mitogenic/metabolic potency ratio of the analogues was found to be inversely correlated with the insulin receptor dissociation rate constant (Kd) in an exponential fashion (r = 0.99), with a disproportionately greater increase in mitogenic potential compared with metabolic potential for analogues with Kd values of less than 40% of that of human insulin. To investigate the molecular mechanisms behind the correlation between the increased half-life of the receptor–ligand complex (low Kd) and mitogenicity, 3 h time-course experiments were performed. Slow ligand dissociation from the insulin receptor induced a parallel sustained activation of the insulin receptor tyrosine kinase. A similar pattern was observed for insulin receptor autophosphorylation and Shc phosphorylation, whereas the duration of insulin receptor substrate-1 phosphorylation with low-Kd analogues and with insulin was similar. Thus the increased half-life of the ligand–receptor complex induces sustained activation of the insulin receptor tyrosine kinase and sustained phoshorylation of Shc, which may be the cause of the disproportionately high mitogenic potency seen for some insulin analogues.

Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity

Cell ◽  
1989 ◽  
Vol 58 (4) ◽  
pp. 631-640 ◽  
Author(s):  
Patrick Auberger ◽  
Laurence Falquerho ◽  
Jean Olivier Contreres ◽  
Gilles Pages ◽  
Ginette Le Cam ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Cdna Cloning ◽  
Receptor Tyrosine Kinase ◽  
Mitogenic Activity ◽  
Insulin Receptor Tyrosine Kinase ◽  
Natural Inhibitor
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