The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2.

ABSTRACT: The insulin signaling pathway is critical in regulating glucose levels and is associated with diabetes, obesity, and longevity. A tyrosine phosphorylation cascade creates docking sites for protein interactions, initiating subsequent propagation of the signal throughout the cell. The phosphotyrosine interactome of this medically important pathway has not yet been studied comprehensively. We therefore applied quantitative interaction proteomics to exhaustively profile all potential phosphotyrosine-dependent interaction sites in its key players. We targeted and compared insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) as central distributors of the insulin signal, the insulin receptor, the insulin-like growth factor 1 receptor, and the insulin receptor-related receptor. Using the stable

SUBMITTER: Hanke S 

PROVIDER: S-EPMC2649814 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature