Research Resource: New and Diverse Substrates for the Insulin Receptor Isoform A Revealed by Quantitative Proteomics After Stimulation With IGF-II or Insulin

摘要: The isoform A of the insulin receptor (IR) (IR-A) is a bifunctional receptor, because it binds both and IGF-II. IR-A activation by IGF-II plays role in development, but its physiological adults unknown. signaling through deregulated cancer favors tumor progression. We hypothesized that binding to elicits unique pathway. In order obtain an unbiased evaluation substrates differentially involved after stimulation, we performed quantitative proteomics recruited tyrosine-phosphorylated protein complexes using stable isotope labeling with amino acids cell culture combination antiphosphotyrosine antibody pull down mass spectrometry. Using cells expressing only human lacking IGF-I identified 38 substrates. Only 10 were known IR mediators, whereas 28 not previously related signaling. Eleven stimulation ligands: two equally insulin, three more strongly IGF-II, six insulin. Moreover, 14 solely 13 stimulation. Interestingly, discoidin domain receptors, migration metastasis, ephrin B4, bidirectional upon cell-cell contact, predominantly activated These findings indicate pathway may play distinct physiology disease.