title: Phosphoproteomic Analyses of Interleukin 2 Signaling Reveal Integrated JAK Kinase-Dependent and -Independent Networks in CD8(+) T Cells.
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.
authors: Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors: Sarah H
authors: SH
authors: Ross
authors: Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors: Christina
authors: C
authors: Rollings
authors: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors: Karen E
authors: KE
authors: Anderson
authors: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors: Phillip T
authors: PT
authors: Hawkins
authors: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors: Len R
authors: LR
authors: Stephens
authors: Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Electronic address: d.a.cantrell@dundee.ac.uk.
authors: Doreen A
authors: DA
authors: Cantrell
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000199:Actins; D007376:Interleukin-2; D020543:Proteome; D012333:RNA, Messenger; D015534:Trans-Activators; D053612:Janus Kinases; D017346:Protein Serine-Threonine Kinases; D020558:GTP Phosphohydrolases