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

Angulo, 2013, Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage, Science, 342, 866, 10.1126/science.1243292 Arenas-Ramirez, 2015, Interleukin-2: biology, design and application, Trends Immunol., 36, 763, 10.1016/j.it.2015.10.003 Arneja, 2014, Qualitatively different T cell phenotypic responses to IL-2 versus IL-15 are unified by identical dependences on receptor signal strength and duration, J. Immunol., 192, 123, 10.4049/jimmunol.1302291 Beadling, 1996, Interleukin-2 activation of STAT5 requires the convergent action of tyrosine kinases and a serine/threonine kinase pathway distinct from the Raf1/ERK2 MAP kinase pathway, EMBO J., 15, 1902, 10.1002/j.1460-2075.1996.tb00541.x Bensinger, 2004, Distinct IL-2 receptor signaling pattern in CD4+CD25+ regulatory T cells, J. Immunol., 172, 5287, 10.4049/jimmunol.172.9.5287 Chamorro, 2001, Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk, BMC Immunol., 2, 3, 10.1186/1471-2172-2-3 Chang, 2008, Phosphorylation at Ser473 regulates heterochromatin protein 1 binding and corepressor function of TIF1beta/KAP1, BMC Mol. Biol., 9, 61, 10.1186/1471-2199-9-61 Chang, 2016, Initiation of T cell signaling by CD45 segregation at ‘close contacts’, Nat. Immunol., 17, 574, 10.1038/ni.3392 Chikuma, 2012, TRIM28 prevents autoinflammatory T cell development in vivo, Nat. Immunol., 13, 596, 10.1038/ni.2293 Clark, 2005, ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events, J. Biol. Chem., 280, 24175, 10.1074/jbc.M414044200 Cornish, 2006, Differential regulation of T-cell growth by IL-2 and IL-15, Blood, 108, 600, 10.1182/blood-2005-12-4827 Couture, 1996, Regulation of the Lck SH2 domain by tyrosine phosphorylation, J. Biol. Chem., 271, 24880, 10.1074/jbc.271.40.24880 Cox, 2008, MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification, Nat. Biotechnol., 26, 1367, 10.1038/nbt.1511 Cunnick, 2002, Regulation of the mitogen-activated protein kinase signaling pathway by SHP2, J. Biol. Chem., 277, 9498, 10.1074/jbc.M110547200 de Aós, 1997, Tyrosine phosphorylation of the CD3-epsilon subunit of the T cell antigen receptor mediates enhanced association with phosphatidylinositol 3-kinase in Jurkat T cells, J. Biol. Chem., 272, 25310, 10.1074/jbc.272.40.25310 Evdokimova, 2006, Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species, Mol. Cell. Biol., 26, 277, 10.1128/MCB.26.1.277-292.2006 Finlay, 2012, PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells, J. Exp. Med., 209, 2441, 10.1084/jem.20112607 Giansanti, 2015, An augmented multiple-protease-based human phosphopeptide atlas, Cell Rep., 11, 1834, 10.1016/j.celrep.2015.05.029 Hatakeyama, 1991, Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association, Science, 252, 1523, 10.1126/science.2047859 Hedrick, 2012, FOXO transcription factors throughout T cell biology, Nat. Rev. Immunol., 12, 649, 10.1038/nri3278 Horak, 1991, T-lymphocyte interleukin 2-dependent tyrosine protein kinase signal transduction involves the activation of p56lck, Proc. Natl. Acad. Sci. USA, 88, 1996, 10.1073/pnas.88.5.1996 Hukelmann, 2016, The cytotoxic T cell proteome and its shaping by the kinase mTOR, Nat. Immunol., 17, 104, 10.1038/ni.3314 John, 1996, An IL-2 response element in the human IL-2 receptor alpha chain promoter is a composite element that binds Stat5, Elf-1, HMG-I(Y) and a GATA family protein, EMBO J., 15, 5627, 10.1002/j.1460-2075.1996.tb00947.x Kim, 2001, The basis for IL-2-induced IL-2 receptor alpha chain gene regulation: importance of two widely separated IL-2 response elements, Immunity, 15, 159, 10.1016/S1074-7613(01)00167-4 Kobayashi, 1993, Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction, Proc. Natl. Acad. Sci. USA, 90, 4201, 10.1073/pnas.90.9.4201 Lee, 2014, Upregulation of eIF5B controls cell-cycle arrest and specific developmental stages, Proc. Natl. Acad. Sci. USA, 111, E4315, 10.1073/pnas.1320477111 Liao, 2013, Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy, Immunity, 38, 13, 10.1016/j.immuni.2013.01.004 Lin, 2012, Critical Role of STAT5 transcription factor tetramerization for cytokine responses and normal immune function, Immunity, 36, 586, 10.1016/j.immuni.2012.02.017 Lu, 2001, Site-specific incorporation of a phosphotyrosine mimetic reveals a role for tyrosine phosphorylation of SHP-2 in cell signaling, Mol. Cell, 8, 759, 10.1016/S1097-2765(01)00369-0 Lucas, 2014, Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency, Nat. Immunol., 15, 88, 10.1038/ni.2771 Luo, 2008, Global impact of oncogenic Src on a phosphotyrosine proteome, J. Proteome Res., 7, 3447, 10.1021/pr800187n Macintyre, 2011, Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism, Immunity, 34, 224, 10.1016/j.immuni.2011.01.012 Maksumova, 2005, Protein tyrosine phosphatase alpha regulates Fyn activity and Cbp/PAG phosphorylation in thymocyte lipid rafts, J. Immunol., 175, 7947, 10.4049/jimmunol.175.12.7947 Marth, 1988, Neoplastic transformation induced by an activated lymphocyte-specific protein tyrosine kinase (pp56lck), Mol. Cell. Biol., 8, 540, 10.1128/MCB.8.2.540 Mitra, 2015, Interleukin-2 activity can be fine tuned with engineered receptor signaling clamps, Immunity, 42, 826, 10.1016/j.immuni.2015.04.018 Mizuno, 2013, Signaling mechanisms and functional roles of cofilin phosphorylation and dephosphorylation, Cell. Signal., 25, 457, 10.1016/j.cellsig.2012.11.001 Najafov, 2012, Akt is efficiently activated by PIF-pocket- and PtdIns(3,4,5)P3-dependent mechanisms leading to resistance to PDK1 inhibitors, Biochem. J., 448, 285, 10.1042/BJ20121287 Navarro, 2011, Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes, Nat. Immunol., 12, 352, 10.1038/ni.2008 Navarro, 2014, Protein kinase D2 is a digital amplifier of T cell receptor-stimulated diacylglycerol signaling in naïve CD8+ T cells, Sci. Signal., 7, ra99, 10.1126/scisignal.2005477 Nika, 2010, Constitutively active Lck kinase in T cells drives antigen receptor signal transduction, Immunity, 32, 766, 10.1016/j.immuni.2010.05.011 O’Shea, 2015, The JAK-STAT pathway: impact on human disease and therapeutic intervention, Annu. Rev. Med., 66, 311, 10.1146/annurev-med-051113-024537 Okkenhaug, 2007, Antigen receptor signalling: a distinctive role for the p110delta isoform of PI3K, Trends Immunol., 28, 80, 10.1016/j.it.2006.12.007 Osinalde, 2011, Interleukin-2 signaling pathway analysis by quantitative phosphoproteomics, J. Proteomics, 75, 177, 10.1016/j.jprot.2011.06.007 Osinalde, 2015, Simultaneous dissection and comparison of IL-2 and IL-15 signaling pathways by global quantitative phosphoproteomics, Proteomics, 15, 520, 10.1002/pmic.201400194 Pipkin, 2010, Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells, Immunity, 32, 79, 10.1016/j.immuni.2009.11.012 Pircher, 1989, Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen, Nature, 342, 559, 10.1038/342559a0 Preston, 2015, Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes, EMBO J., 34, 2008, 10.15252/embj.201490252 Ray, 2015, The interleukin-2-mTORc1 kinase axis defines the signaling, differentiation, and metabolism of T helper 1 and follicular B helper T cells, Immunity, 43, 690, 10.1016/j.immuni.2015.08.017 Safari, 2011, Mammalian Pragmin regulates Src family kinases via the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif that is exploited by bacterial effectors, Proc. Natl. Acad. Sci. USA, 108, 14938, 10.1073/pnas.1107740108 Smith, 2016, Essential biphasic role for JAK3 catalytic activity in IL-2 receptor signaling, Nat. Chem. Biol., 12, 373, 10.1038/nchembio.2056 Spangler, 2015, Antibodies to interleukin-2 elicit selective T cell subset potentiation through distinct conformational mechanisms, Immunity, 42, 815, 10.1016/j.immuni.2015.04.015 Stone, 2015, ICOS coreceptor signaling inactivates the transcription factor FOXO1 to promote Tfh cell differentiation, Immunity, 42, 239, 10.1016/j.immuni.2015.01.017 Tanaka, 1995, Chicken alpha-enolase but not beta-enolase has a Src-dependent tyrosine-phosphorylation site: cDNA cloning and nucleotide sequence analysis, J. Biochem., 117, 554, 10.1093/oxfordjournals.jbchem.a124743 Titz, 2010, The proximal signaling network of the BCR-ABL1 oncogene shows a modular organization, Oncogene, 29, 5895, 10.1038/onc.2010.331 Vindis, 2004, EphB1-mediated cell migration requires the phosphorylation of paxillin at Tyr-31/Tyr-118, J. Biol. Chem., 279, 27965, 10.1074/jbc.M401295200 Zhang, 2003, The role of C-terminal tyrosine phosphorylation in the regulation of SHP-1 explored via expressed protein ligation, J. Biol. Chem., 278, 4668, 10.1074/jbc.M210028200 Zhou, 2000, Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation, Mol. Cell. Biol., 20, 4371, 10.1128/MCB.20.12.4371-4380.2000