scholarly journals Insulin resistance and muscle insulin receptor substrate-1 serine hyperphosphorylation

2014 ◽  
Vol 2 (12) ◽  
pp. e12236 ◽  
Author(s):  
Charles A. Stuart ◽  
Mary E. A. Howell ◽  
Brian M. Cartwright ◽  
Melanie P. McCurry ◽  
Michelle L. Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1

scholarly journals Serine Phosphorylation Proximal to Its Phosphotyrosine Binding Domain Inhibits Insulin Receptor Substrate 1 Function and Promotes Insulin Resistance

2004 ◽  
Vol 24 (21) ◽  
pp. 9668-9681 ◽  
Author(s):  
Yan-Fang Liu ◽  
Avia Herschkovitz ◽  
Sigalit Boura-Halfon ◽  
Denise Ronen ◽  
Keren Paz ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Insulin Treatment ◽  
Binding Domain ◽  
Serine Phosphorylation ◽  
Insulin Receptor Substrate ◽  
Control Mechanisms ◽  
Insulin Receptor Substrate 1 ◽  
Phosphotyrosine Binding Domain

ABSTRACT Ser/Thr phosphorylation of insulin receptor substrate (IRS) proteins negatively modulates insulin signaling. Therefore, the identification of serine sites whose phosphorylation inhibit IRS protein functions is of physiological importance. Here we mutated seven Ser sites located proximal to the phosphotyrosine binding domain of insulin receptor substrate 1 (IRS-1) (S265, S302, S325, S336, S358, S407, and S408) into Ala. When overexpressed in rat hepatoma Fao or CHO cells, the mutated IRS-1 protein in which the seven Ser sites were mutated to Ala (IRS-17A), unlike wild-type IRS-1 (IRS-1WT), maintained its Tyr-phosphorylated active conformation after prolonged insulin treatment or when the cells were challenged with inducers of insulin resistance prior to acute insulin treatment. This was due to the ability of IRS-17A to remain complexed with the insulin receptor (IR), unlike IRS-1WT, which underwent Ser phosphorylation, resulting in its dissociation from IR. Studies of truncated forms of IRS-1 revealed that the region between amino acids 365 to 430 is a main insulin-stimulated Ser phosphorylation domain. Indeed, IRS-1 mutated only at S408, which undergoes phosphorylation in vivo, partially maintained the properties of IRS-17A and conferred protection against selected inducers of insulin resistance. These findings suggest that S408 and additional Ser sites among the seven mutated Ser sites are targets for IRS-1 kinases that play a key negative regulatory role in IRS-1 function and insulin action. These sites presumably serve as points of convergence, where physiological feedback control mechanisms, which are triggered by insulin-stimulated IRS kinases, overlap with IRS kinases triggered by inducers of insulin resistance to terminate insulin signaling.

scholarly journals Regulation of insulin receptor substrate-1 in liver and muscle of animal models of insulin resistance.

1992 ◽  
Vol 90 (5) ◽  
pp. 1839-1849 ◽  
Author(s):  
M J Saad ◽  
E Araki ◽  
M Miralpeix ◽  
P L Rothenberg ◽  
M F White ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Animal Models ◽  
Insulin Receptor ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1

scholarly journals Amelioration of insulin resistance in women with PCOS via reduced insulin receptor substrate-1 Ser312 phosphorylation following laparoscopic ovarian electrocautery

2007 ◽  
Vol 22 (4) ◽  
pp. 1003-1010 ◽  
Author(s):  
Kok-Min Seow ◽  
Chi-Chang Juan ◽  
Yung-Pei Hsu ◽  
Jiann-Loung Hwang ◽  
Lee-Wen Huang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Insulin Receptor Substrate ◽  
Insulin Receptor Substrate 1
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