Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics

► Global tyrosine phosphoproteome triggered by IL-2 in human lymphocytes was characterized. ► Molecular snapshot of IL-2 signaling led to identification of 172 phosphotyrosine effectors. ► Combinatorial site-specific phosphoproteomic analysis resulted in identification of 99 phosphorylated sites. ► Chemical inhibition of the analyzed IL-2-mediated signaling branches had distinct effects on lymphocyte proliferation.