Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action
Harvard University · Howard Hughes Medical Institute · +1 more institution
Abstract
Serine phosphorylation of insulin receptor substrate-1 (IRS-1) inhibits insulin signal transduction in a variety of cell backgrounds, which might contribute to peripheral insulin resistance. However, because of the large number of potential phosphorylation sites, the mechanism of inhibition has been difficult to determine. One serine residue located near the phosphotyrosine-binding (PTB) domain in IRS-1 (Ser307in rat IRS-1 or Ser312 in human IRS-1) is phosphorylated via several mechanisms, including insulin-stimulated kinases or stress-activated kinases like JNK1. During a yeast tri-hybrid assay, phosphorylation of Ser307 by JNK1 disrupted the interaction between the catalytic domain of the insulin receptor…
Citation impact
- FWCI
- 15.41
- Percentile
- 100%
- References
- 55
Authors
6- VAVincent Aguirre
Harvard University, Howard Hughes Medical Institute, Joslin Diabetes Center
- EDEric D. Werner
Howard Hughes Medical Institute, Harvard University, Joslin Diabetes Center
- JGJodel Giraud
Harvard University, Howard Hughes Medical Institute, Joslin Diabetes Center
- YHYong Hee Lee
Joslin Diabetes Center, Howard Hughes Medical Institute, Harvard University
- SSSteve Shoelson
Joslin Diabetes Center, Harvard University, Howard Hughes Medical Institute
Topics & keywords
- Insulin receptor
- Insulin receptor substrate
- IRS2
- Phosphorylation
- Phosphotyrosine-binding domain
- GRB10
- Phosphorylation cascade
- IRS1