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 journalArticle

30 Citations (Scopus)
273 Downloads (Pure)

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

Fingerprint Dive into the research topics of 'Phosphoproteomic Analyses of Interleukin 2 Signaling Reveal Integrated JAK Kinase-Dependent and -Independent Networks in CD8+ T Cells'. Together they form a unique fingerprint.

  • Student Theses

    The role of JAK1 and JAK3 in CD8+ effector T cells

    Author: Rollings, C., 2016

    Supervisor: Cantrell, D. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

    Profiles

    No photo of Doreen Cantrell

    Cantrell, Doreen

    Person: Academic

    Cite this