Phosphoproteomic Analyses of Interleukin 2 Signaling Reveal Integrated JAK Kinase-Dependent and -Independent Networks in CD8+ T Cells

Sarah H. Ross, Christina Rollings, Karen E. Anderson, Phillip T. Hawkins, Len R. Stephens, Doreen A. Cantrell (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)
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Abstract

Interleukin-2 (IL-2) is a fundamental cytokine that controls proliferation and differentiation of T cells. Here, we used high-resolution mass spectrometry to generate a comprehensive and detailed map of IL-2 protein phosphorylations in cytotoxic T cells (CTL). The data revealed that Janus kinases (JAKs) couple IL-2 receptors to the coordinated phosphorylation of transcription factors, regulators of chromatin, mRNA translation, GTPases, vesicle trafficking, and the actin and microtubule cytoskeleton. We identified an IL-2-JAK-independent SRC family Tyr-kinase-controlled signaling network that regulates ∼10% of the CTL phosphoproteome, the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), and the activity of the serine/threonine kinase AKT. These data reveal a signaling framework wherein IL-2-JAK-controlled pathways coordinate with IL-2-independent networks of kinase activity and provide a resource toward the further understanding of the networks of protein phosphorylation that program CTL fate.

Original languageEnglish
Pages (from-to)685-700
Number of pages16
JournalImmunity
Volume45
Issue number3
Early online date23 Aug 2016
DOIs
Publication statusPublished - 20 Sep 2016

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