Insulin responsive substrate

After the insulin receptor catalyzes its own phosphorylation, the receptor is activated in a way that provokes it to phosphoiylate other proteins. The main substrate is a cytoplasmic protein called IRS. IKS stands for insulin responsive substrate. IRS has a molecular weight of 131,00(1 (131 kDa). The phosphorylation of IRS is represented by (Mothe and Obberghen, 1996) ... 

Insulin responsive substrate (iRS), 179 integrins, 135-136, 339,534 Iniecnal elastic lamina, 359, 360 Intervention study, 964 Intestinal tract... 

Guanosine triphosphate Hemoglobin High-density lipoprotein Inositol-l,4,5-trisphosphate Insulin-responsive substrate ... 

Activation of the enzyme PIS kinase (PI3K) constitutes a third pathway of Trk receptor signaling. The precise mechanism by which PI3K activation occurs has not yet been completely elucidated, but appears to involve Trk activation of intermediate proteins, such as insulin receptor substrate (IRS)-1,2 and the IRS-like protein Gabl. Downstream of PI3K activation is stimulation of the kinase Akt, which is largely responsible for the survival effects mediated by this pathway. 

Signal transduction The binding of insulin to the a-subunits of the insulin receptor induces conformational changes that are transduced to the 3-subunits. This promotes a rapid autophosphorylation of a specific tyrosine residue on each 3-subunit (see Figure 23.7). Autophosphorylation initiates a cascade of cellsignaling responses, including phosphorylation of a family of pro teins called insulin receptor substrate (IRS) proteins. At least four... 

The phenotype of mice deficient in IRS-1 indicated that other docking molecules and substrates must be involved in insulin signalling.34 IRS-1-deficient mice were stunted in their growth and had impaired glucose tolerance, but the absence of IRS-1 did not completely eliminate the response to insulin. The need for another IRS also became apparent from the phenotypes of mice carrying insulin receptor mutants. A more likely candidate as primary substrate of the insulin receptor is IRS-2. In contrast to mice deficient in IRS-1, mice that lack the insulin receptor substrate-2 gene are hj erglycaemic and... 

T. Doenst, G. W. Goodwin, A. M. Cedars, M. Wang, S. Stepkowski, and H. Taegtmeyer, Load-induced changes in vivo alter substrate fluxes and insulin responsiveness of rat heart in vitro, Metabolism 50, 1083-1090 (2001). 

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