Mechanisms of type-I- and type-II-interferon-mediated signalling (original) (raw)

• Pestka, S., Langer, J. A., Zoon, K. C. & Samuel, C. E. Interferons and their actions. Annu. Rev. Biochem. 56, 727–777 (1987).
  Article CAS PubMed Google Scholar
• Pestka, S., Krause, C. D. & Walter, M. R. Interferons, interferon-like cytokines, and their receptors. Immunol. Rev. 202, 8–32 (2004).
  Article CAS PubMed Google Scholar
• Pestka, S. The human interferon α species and hybrid proteins. Semin. Oncol. 24, S9-4–S9-17 (1997).
  Google Scholar
• Chen, J., Baig, E. & Fish, E. N. Diversity and relatedness among the type I interferons. J. Interfon Cytokine Res. 24, 687–698 (2004).
  Article CAS Google Scholar
• Platanias, L. C. & Fish, E. N. Signaling pathways activated by interferons. Exp. Hematol. 27, 1583–1592 (1999).
  Article CAS PubMed Google Scholar
• Parmar, S. & Platanias, L. C. Interferons: mechanisms of action and clinical applications. Curr. Opin. Oncol. 15, 431–439 (2003).
  Article CAS PubMed Google Scholar
• Pestka, S. et al. The interferon γ (IFN-γ) receptor: a paradigm for the multichain cytokine receptor. Cytokine Growth Factor Rev. 8, 189–206 (1997).
  Article CAS PubMed Google Scholar
• Bach, E. A., Aguet, M. & Schreiber, R. D. The IFN γ receptor: a paradigm for cytokine receptor signaling. Annu. Rev. Immunol. 15, 563–591 (1997).
  Article CAS PubMed Google Scholar
• Isaacs, A. & Lindenmann, J. Virus interference. I. The interferon. Proc. R. Soc. Lond. B 147, 258–267 (1957).
  Article CAS PubMed Google Scholar
• Kotenko, S. V. et al. IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nature Immunol. 4, 69–77 (2003).
  Article CAS Google Scholar
• Darnell, J. E., Kerr, I. M. & Stark, G. R. Jak–STAT pathways and transcriptional activation in response to IFNs and other extracellular proteins. Science 264, 1415–1420 (1994). A comprehensive review of the IFN-activated JAK–STAT-signalling pathways.
  Article CAS PubMed Google Scholar
• Ihle, J. N. The Janus protein tyrosine kinase family and its role in cytokine signaling. Adv. Immunol. 60, 1–35 (1995).
  Article CAS PubMed Google Scholar
• Platanias, L. C. The p38 mitogen-activated protein kinase pathway and its role in interferon signaling. Pharmacol. Ther. 98, 129–142 (2003).
  Article CAS PubMed Google Scholar
• Der, S. D., Zhou, A., Williams, B. R. & Silverman, R. H. Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays. Proc. Natl Acad. Sci. USA 95, 15623–15628 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Schindler, C., Shuai, K., Prezioso, V. R. & Darnell, J. E. Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 257, 809–813 (1992).
  Article CAS PubMed Google Scholar
• Fu, X. Y., Schindler, C., Improta, T., Aebersold, R. & Darnell, J. E. The proteins of ISGF-3, the interferon α-induced transcriptional activator, define a gene family involved in signal transduction. Proc. Natl Acad. Sci. USA 89, 7840–7843 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Shuai, K., Schindler, C., Prezioso, V. R. & Darnell, J. E. Activation of transcription by IFN-γ: tyrosine phosphorylation of a 91-kD DNA binding protein. Science 258, 1808–1812 (1992).
  Article CAS PubMed Google Scholar
• Silvennoinen, O., Ihle, J. N., Schlessinger, J. & Levy, D. E. Interferon-induced nuclear signaling by Jak protein tyrosine kinases. Nature 366, 583–585 (1993).
  Article CAS PubMed Google Scholar
• Stark, G. R., Kerr, I. M., Williams, B. R. G., Silverman, R. H. & Schreiber, R. D. How cells respond to interferons. Annu. Rev. Biochem. 67, 227–264 (1998).
  Article CAS PubMed Google Scholar
• Darnell, J. E. Stats and gene regulation. Science 277, 1630–1635 (1997). An excellent review of the mechanisms of STAT activation and the regulatory effects of STATs on gene transcription.
  Article CAS PubMed Google Scholar
• Aaronson, D. S. & Horvath C. M. A road map for those who don't know JAK–STAT. Science 296, 1653–1655 (2002).
  Article CAS PubMed Google Scholar
• Meinke, A., Barahmand-Pour, F., Wohrl, S., Stoiber, D. & Decker, T. Activation of different Stat5 isoforms contributes to cell-type-restricted signaling in response to interferons. Mol. Cell. Biol. 16, 6937–6944 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Farrar, J. D., Smith, J. D., Murphy, T. L. & Murphy, K. M. Recruitment of Stat4 to the human interferon-α/β receptor requires activated Stat2. J. Biol. Chem. 275, 2693–2697 (2000).
  Article CAS PubMed Google Scholar
• Torpey, N., Maher, S. E., Bothwell, A. L. & Pober, J. S. Interferon α but not interleukin 12 activates STAT4 signaling in human vascular endothelial cells. J. Biol. Chem. 279, 26789–26796 (2004).
  Article CAS PubMed Google Scholar
• Matikainen, S. et al. Interferon-α activates multiple STAT proteins and upregulates proliferation-associated _IL-2R_α, c-myc, and pim-1 genes in human T cells. Blood 93, 1980–1991 (1999).
  Article CAS PubMed Google Scholar
• Fasler-Kan, E., Pansky, A., Wiederkehr, M., Battegay, M. & Heim, M. H. Interferon-α activates signal transducers and activators of transcription 5 and 6 in Daudi cells. Eur. J. Biochem. 254, 514–519 (1998).
  Article CAS PubMed Google Scholar
• Nguyen, K. B. et al. Critical role for STAT4 activation by type 1 interferons in the interferon-γ response to viral infection. Science 297, 2063–2066 (2002).
  Article CAS PubMed Google Scholar
• Boehm, U., Klamp, T., Groot, M. & Howard, J. C. Cellular responses to interferon-γ. Annu. Rev. Immunol. 15, 749–795 (1997).
  Article CAS PubMed Google Scholar
• Wen, Z., Zhong, Z. & Darnell, J. E. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82, 241–250 (1995).
  Article CAS PubMed Google Scholar
• Wen, Z. & Darnell, J. E. Mapping of Stat3 serine phosphorylation to a single residue (727) and evidence that serine phosphorylation has no influence on DNA binding of Stat1 and Stat3. Nucleic Acids Res. 25, 2062–2067 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Varinou, L. et al. Phosphorylation of the Stat1 transactivation domain is required for full-fledged IFN-γ-dependent innate immunity. Immunity 19, 793–802 (2003).
  Article CAS PubMed Google Scholar
• Uddin, S. et al. Protein kinase C-δ (PKC-δ) is activated by type I interferons and mediates phosphorylation of Stat1 on serine 727. J. Biol. Chem. 277, 14408–14416 (2002). The first identification of PKC-δ as an IFN-activated kinase that regulates the phosphorylation of STAT1 on Ser727.
  Article CAS PubMed Google Scholar
• Deb, D. K. et al. Activation of protein kinase C δ by IFN-γ. J. Immunol. 171, 267–273 (2003).
  Article CAS PubMed Google Scholar
• Kristof, A. S., Marks-Konczalik, J., Billings, E. & Moss, J. Stimulation of signal transducer and activator of transcription-1 (STAT1)-dependent gene transcription by lipopolysaccharide and interferon-γ is regulated by mammalian target of rapamycin. J. Biol. Chem. 278, 33637–33644 (2003).
  Article CAS PubMed Google Scholar
• Choudhury, G. G. A linear signal transduction pathway involving phosphatidylinositol 3-kinase, protein kinase C-ε, and MAPK in mesangial cells regulates interferon-γ-induced STAT1α transcriptional activation. J. Biol. Chem. 279, 27399–27409 (2004).
  Article CAS PubMed Google Scholar
• Nair, J. S. et al. Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-γ. Proc. Natl Acad. Sci. USA 99, 5971–5976 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, J. J. et al. Two contact regions between Stat1 and CBP/p300 in interferon γ signaling. Proc. Natl Acad. Sci. USA 93, 15092–15096 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Bhattacharya, S. et al. Cooperation of Stat2 and p300/CBP in signaling induced by interferon-α. Nature 383, 344–347 (1996).
  Article CAS PubMed Google Scholar
• Zhang, J. J. et al. Ser727-dependent recruitment of MCM5 by Stat1α in IFN-γ-induced transcriptional activation. EMBO J. 17, 6963–6971 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• DaFonseca, C. J., Shu, F. & Zhang, J. J. Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-γ. Proc. Natl Acad. Sci. USA 98, 3034–3039 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Hebbes, T. R., Thorne, A. W. & Crane-Robinson, C. A direct link between core histone acetylation and transcriptionally active chromatin. EMBO J. 7, 1395–1402 (1988).
  Article CAS PubMed PubMed Central Google Scholar
• Paulson, M., Press, C., Smith, E., Tanese, E. & Levy, D. E. IFN-stimulated transcription through a TBP- free acetyltransferase complex escapes viral shutoff. Nature Cell Biol. 4, 140–147 (2002).
  Article CAS PubMed Google Scholar
• Huang, M. et al. Chromatin-remodelling factor BRG1 selectively activates a subset of interferon-α-inducible genes. Nature Cell Biol. 4, 774–781 (2002).
  Article CAS PubMed Google Scholar
• Zhu, M., John, S., Berg, M. & Leonard, W. J. Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNγ-mediated signaling. Cell 96, 121–130 (1999).
  Article CAS PubMed Google Scholar
• Nusinzon, I. & Horvath, C. M. Interferon-stimulated transcription and innate antiviral immunity require deacetylase activity and histone deacetylase 1. Proc. Natl Acad. Sci. USA 100, 14742–14747 (2003). The first evidence that histone-deacetylase activity is required for IFN-dependent transcription.
  Article CAS PubMed PubMed Central Google Scholar
• Chang, H. M. et al. Induction of interferon-stimulated gene expression and antiviral responses require protein deacetylase activity. Proc. Natl Acad. Sci. USA 101, 9578–9583 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Sakamoto, S., Potla, R. & Larner, A. C. Histone deacetylase activity is required to recruit RNA polymerase II to the promoters of selected interferon-stimulated early response genes. J. Biol. Chem. 279, 40362–40367 (2004).
  Article CAS PubMed Google Scholar
• Mayer, B. J., Hamaguchi, M. & Hanafusa, H. A novel viral oncogene with structural homology to phospholipase C. Nature 332, 272–275 (1988).
  Article CAS PubMed Google Scholar
• Feller, S. M. Crk family adaptors — signaling complex formation and biological roles. Oncogene 20, 6348–6371 (2001).
  Article CAS PubMed Google Scholar
• Ahmad, S., Alsayed, Y., Druker, B. J. & Platanias, L. C. The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein. J. Biol. Chem. 272, 29991–29994 (1997).
  Article CAS PubMed Google Scholar
• Alsayed, Y. et al. Interferon-γ activates the C3G/Rap1 signaling pathway. J. Immunol. 164, 1800–1806 (2000).
  Article CAS PubMed Google Scholar
• Stork, P. J. Does Rap1 deserve a bad Rap? Trends Biochem. Sci. 28, 267–275 (2003).
  Article CAS PubMed Google Scholar
• Bos, J. L., de Rooij, J. & Reedquist, K. A. Rap1 signaling: adhering to new models. Nature Rev. Mol. Cell Biol. 2, 369–377 (2001).
  Article CAS Google Scholar
• Kitayama, H., Sugimoto, Y., Matsuzaki, T., Ikawa, Y. & Noda, M. A _ras_-related gene with transformation suppressor activity. Cell 56, 77–84 (1989).
  Article CAS PubMed Google Scholar
• Schmitt, J. M. & Stork, P. J. Cyclic AMP-mediated inhibition of cell growth requires the small G protein Rap1. Mol. Cell. Biol. 21, 3671–3683 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Lahlou, H. et al. sst2 Somatostatin receptor inhibits cell proliferation through Ras-, Rap1-, and B-Raf-dependent ERK2 activation. J. Biol. Chem. 278, 39356–39371 (2003).
  Article CAS PubMed Google Scholar
• Hattori, M. & Minato, N. Rap1 GTPase: functions, regulation and malignancy. J. Biochem. 134, 479–484 (2003).
  Article CAS PubMed Google Scholar
• Lekmine, F. et al. The CrkL adapter protein is required for type I interferon-dependent gene transcription and activation of the small G-protein Rap1. Biochem. Biophys. Res. Commun. 291, 744–750 (2002).
  Article CAS PubMed Google Scholar
• Platanias, L. C. et al. CrkL and CrkII participate in the generation of the growth inhibitory effects of interferons on primary hematopoietic progenitors. Exp. Hematol. 27, 1315–1321 (1999).
  Article CAS PubMed Google Scholar
• Huang, C. C., You, J. L., Wu, M. Y. & Hsu, K. S. Rap1-induced p38 mitogen-activated protein kinase activation facilitates AMPA receptor trafficking via the GDI•Rab5 complex. Potential role in (S)-3,5-dihydroxyphenylglycene-induced long-term depression. J. Biol. Chem. 279, 12286–12292 (2004).
  Article CAS PubMed Google Scholar
• Katagiri, K. et al. Crucial functions of the Rap1 effector molecule RAPL in lymphocyte and dendritic cell trafficking. Nature Immunol. 5, 1045–1051 (2004).
  Article CAS Google Scholar
• Fish, E. N. et al. Activation of a CrkL–Stat5 signaling complex by type I interferons. J. Biol. Chem. 274, 571–573 (1999). The first report that CRKL forms DNA-binding complexes with STAT5 and functions as a nuclear adaptor for STAT5 in type-I-IFN-mediated signalling.
  Article CAS PubMed Google Scholar
• Grumbach, I. M. et al. Engagement of the CrkL adapter in interferon α signaling in BCR–ABL expressing cells. Br. J. Haematol. 112, 327–336 (2001).
  Article CAS PubMed Google Scholar
• Takahashi, Y., Lallemand-Breitenbach, V., Zhu, J. & de The, H. PML nuclear bodies and apoptosis. Oncogene 23, 2819–2824 (2004).
  Article CAS PubMed Google Scholar
• Uddin, S. et al. Role of Stat5 in type I interferon-signaling and transcriptional regulation. Biochem. Biophys. Res. Commun. 308, 325–330 (2003).
  Article CAS PubMed Google Scholar
• Schaeffer, H. J. & Weber, M. J. Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol. Cell. Biol. 19, 2435–2444 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Chang, L. & Karin, M. Mammalian MAP kinase signaling cascades. Nature 410, 37–40 (2001).
  Article CAS PubMed Google Scholar
• Dong, C., Davis, R. J. & Flavell, R. A. MAP kinases in the immune response. Annu. Rev. Immunol. 20, 55–72 (2002).
  Article CAS PubMed Google Scholar
• Hazzalin, C. A. & Mahadevan, L. C. MAPK-regulated transcription: a continuously variable gene switch? Nature Rev. Mol. Cell Biol. 3, 30–40 (2002).
  Article CAS Google Scholar
• Platanias, L. C. Map kinase signaling pathways and hematologic malignancies. Blood 101, 4667–4679 (2003).
  Article CAS PubMed Google Scholar
• Uddin, S. et al. Activation of the p38 Map kinase by type I interferons. J. Biol. Chem. 274, 30127–30131 (1999).
  Article CAS PubMed Google Scholar
• Goh, K. C., Haque, S. J. & Williams, B. R. p38 MAP kinase is required for STAT1 serine phosphorylation and transcriptional activation induced by interferons. EMBO J. 18, 5601–5608 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Uddin, S. et al. The Rac1/p38 Map kinase pathway is required for IFNα-dependent transcriptional activation but not serine phosphorylation of Stat-proteins. J. Biol. Chem. 275, 27634–27640 (2000).
  Article CAS PubMed Google Scholar
• Kovarik, P. et al. Stress-induced phosphorylation of Stat1 at Ser727 requires p38 mitogen-activated protein kinase whereas IFN-γ uses a different pathway. Proc. Natl Acad. Sci. USA 96, 13956–13961 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Li, Y. et al. Role of p38α Map kinase in type I interferon signaling. J. Biol. Chem. 279, 970–979 (2004). Definitive evidence that the type-I-IFN-activated p38-signalling pathway is required for transcriptional regulation.
  Article CAS PubMed Google Scholar
• Ramsauer, K. et al. p38 MAPK enhances STAT1-dependent transcription independently of Ser-727 phosphorylation. Proc. Natl Acad. Sci. USA 99, 12859–12864 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Crespo, P., Schuebel, K. E., Ostrom, A. A., Gutkind, J. S. & Bustelo, X. R. Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product. Nature 385, 169–172 (1997).
  Article CAS PubMed Google Scholar
• Bustelo, X. R. Regulatory and signaling properties of the Vav family. Mol. Cell. Biol. 20, 1461–1477 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Platanias, L. C. & Sweet, M. E. Interferon α induces rapid tyrosine phosphorylation of the vav proto-oncogene product in hematopoietic cells. J. Biol. Chem. 269, 3143–3146 (1994).
  Article CAS PubMed Google Scholar
• Micouin, A., Wietzrbin, J., Steunou, V. & Martyre, M. C. p95Vav is associated to the IFNα/β receptor and contributes to the antiproliferative effect of IFNα in megacaryocytic cell lines. Oncogene 19, 387–394 (2000).
  Article CAS PubMed Google Scholar
• Uddin, S., Sweet, M. E., Colamonici, O. R., Krolewski, J. J. & Platanias, L. C. The vav proto-oncogene product interacts with the Tyk-2 tyrosine kinase. FEBS Lett. 403, 31–34 (1997).
  Article CAS PubMed Google Scholar
• Li, Y. et al. Activation of Mkk3 and Mkk6 by type I interferons. J. Biol. Chem. 280, 10001–10010 (2005).
  Article CAS PubMed Google Scholar
• Kotlyarov, A. & Gaestel, M. Is MK2 (mitogen-activated protein kinase-activated protein kinase 2) the key for understanding post-transcriptional regulation of gene expression? Biochem. Soc. Trans. 30, 959–963 (2002).
  Article CAS PubMed Google Scholar
• Deak, M., Clifton A. D., Lucocq, L. M. & Alessi, D. R. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J. 17, 4426–4441 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Soloaga, A. et al. MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of histone H3 and HMG-14. EMBO J. 22, 2788–2797 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Clayton, A. L. & Mahadevan, L. C. MAP kinase-mediated phosphoacetylation of histone H3 and inducible gene regulation. FEBS Lett. 546, 51–58 (2003).
  Article CAS PubMed Google Scholar
• Waskiewicz, A. J., Flynn, A., Proud, C. G. & Cooper, J. A. Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J. 16, 1909–1920 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Knauf, U., Tschopp, C. & Gram, H. Negative regulation of protein translation by mitogen-activated protein kinase-interacting kinases 1 and 2. Mol. Cell. Biol. 21, 5500–5511 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Mayer, I. A. et al. The p38 MAPK pathway mediates the growth inhibitory effects of interferon-α in BCR–ABL-expressing cells. J. Biol. Chem. 276, 28570–28577 (2001).
  Article CAS PubMed Google Scholar
• Verma, A. et al. Activation of the p38 Map kinase pathway mediates the suppressive effects of type I interferons and transforming growth factor β on normal hematopoiesis. J. Biol. Chem. 277, 7726–7735 (2002).
  Article CAS PubMed Google Scholar
• Ishida, H. et al. Involvement of p38 signaling pathway in interferon-α-mediated antiviral activity towards hepatitis C virus. Biochem. Biophys. Res. Commun. 321, 722–727 (2004).
  Article CAS PubMed Google Scholar
• Katze, M. G., He, Y. & Gale, M. Viruses and interferon: a fight for supremacy. Nature Rev. Immunol. 2, 675–687 (2002). An excellent review of the mechanisms by which IFNs mediate antiviral effects.
  Article CAS Google Scholar
• David, M. et al. Requirement for MAP kinase (ERK2) activity in interferon α- and interferon β-stimulated gene expression through STAT proteins. Science 269, 1721–1723 (1995).
  Article CAS PubMed Google Scholar
• Hu, J. et al. ERK1 and ERK2 activate CCAAAT/enhancer-binding protein-β-dependent gene transcription in response to interferon-γ. J. Biol. Chem. 276, 287–297 (2001).
  Article CAS PubMed Google Scholar
• Wang, F. et al. Disruption of Erk-dependent type I interferon induction breaks the myxoma virus species barrier. Nature Immunol. 5, 1266–1274 (2004).
  Article CAS Google Scholar
• Roy, S. K. et al. MEKK1 plays a critical role in activating the transcription factor C/EBP-β-dependent gene expression in response to IFN-γ. Proc. Natl Acad. Sci. USA 99, 7945–7950 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Roy, S. K., Wachira, S. J., Weihua, X., Hu, J. & Kalvakolanu, D. V. CCAAT/enhancer-binding protein-β regulates interferon-induced transcription through a novel element. J. Biol. Chem. 275, 12626–12632 (2000).
  Article CAS PubMed Google Scholar
• Floyd, Z. E. & Stephens, J. M. Interferon-γ-mediated activation and ubiquitin-proteasome-dependent degradation of PPARγ in adipocytes. J. Biol. Chem. 277, 4062–4068 (2002).
  Article CAS PubMed Google Scholar
• Li, C. et al. IFNα induces Fas expression and apoptosis in hedgehog pathway activated BCC cells through inhibiting Ras–Erk signaling. Oncogene 23, 1608–1617 (2004).
  Article CAS PubMed Google Scholar
• Li, G., Xiang, Y., Sabapathy, K. & Silverman, R. H. An apoptotic signaling pathway in the interferon antiviral response mediated by RNase L and c-Jun NH2-terminal kinase. J. Biol. Chem. 279, 1123–1131 (2004).
  Article CAS PubMed Google Scholar
• Uddin, S. et al. Interferon-α engages the insulin receptor substrate-1 to associate with the phosphatidylinositol 3′-kinase. J. Biol. Chem. 270, 15938–159341 (1995).
  Article CAS PubMed Google Scholar
• White, M. F. Insulin signaling in health and disease. Science 302, 1710–1711 (2003).
  Article CAS PubMed Google Scholar
• Platanias, L. C. et al. The type I interferon receptor mediates tyrosine phosphorylation of insulin receptor substrate 2. J. Biol. Chem. 271, 278–282 (1996).
  Article CAS PubMed Google Scholar
• Burfoot, M. S. et al. Janus kinase-dependent activation of insulin receptor substrate 1 in response to interleukin-4, oncostatin M, and the interferons. J. Biol. Chem. 272, 24183–24190 (1997).
  Article CAS PubMed Google Scholar
• Uddin, S. et al. The IRS-pathway operates distinctively from the Stat-pathway in hematopoietic cells and transduces common and distinct signals during engagement of the insulin or interferon-α receptors. Blood 90, 2574–2582 (1997).
  CAS PubMed Google Scholar
• Uddin, S. et al. Interferon-dependent activation of the serine kinase PI 3′-kinase requires engagement of the IRS pathway but not the Stat pathway. Biochem. Biophys. Res. Commun. 270, 158–162 (2000).
  Article CAS PubMed Google Scholar
• Uddin, S. et al. Activation of the phosphatidylinositol 3-kinase serine kinase by IFN-α. J. Immunol. 158, 2390–2397 (1997).
  CAS PubMed Google Scholar
• Cengel, K. A. & Freund, G. G. JAK1-dependent phosphorylation of insulin receptor substrate-1 (IRS-1) is inhibited by IRS-1 serine phosphorylation. J. Biol. Chem. 274, 27969–27974 (1999).
  Article CAS PubMed Google Scholar
• Nguyen, H., Ramana, C. V., Bayes, J. & Stark, G. R. Roles of phosphatidylinositol 3-kinase in interferon-γ-dependent phosphorylation of STAT1 on serine 727 and activation of gene expression. J. Biol. Chem. 276, 33361–33368 (2001).
  Article CAS PubMed Google Scholar
• DeVries, T. A., Rachelle, L., Kalkofen, A., Matassa, A. & Reyland, M. E. Protein kinase Cδ regulates apoptosis via activation of STAT1. J. Biol. Chem. 279, 45603–45612 (2004).
  Article CAS PubMed Google Scholar
• Lu, Z. et al. Tumor promotion by depleting cells of protein kinase C-δ. Mol. Cell. Biol. 17, 3418–3428 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Redding, P. J. et al. Transgenic mice overexpressing protein kinase C δ in the epidermis are resistant to skin tumor promotion by 12-_O_-tetradecanoylphorbol-13-acetate. Cancer Res. 59, 5710–5718 (1999).
  Google Scholar
• Srivastava, K. K. et al. Engagement of protein kinase C-θ in interferon signaling in T-cells. J. Biol. Chem. 279, 29911–29920 (2004).
  Article CAS PubMed Google Scholar
• Vivanco, I. & Sawyers, C. L. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nature Rev. Cancer 2, 489–501 (2002).
  Article CAS Google Scholar
• Barca, O. et al. Interferon β promotes survival in primary astrocytes through phosphatidylinositol 3-kinase. J. Neuroimmunol. 139, 155–159 (2003).
  Article CAS PubMed Google Scholar
• Ruuth, K., Carlsson, L., Hallberg, B. & Lundgren, E. Interferon-α promotes survival of human primary B-lymphocytes via phosphatidylinositol 3-kinase. Biochem. Biophys. Res. Commun. 284, 583–586 (2001).
  Article CAS PubMed Google Scholar
• Wang, K. et al. Inhibition of neutrophil apoptosis by type 1 IFN depends on cross-talk between phosphoinositol 3-kinase, protein kinase C-δ, and NF-κB signaling pathways. J. Immunol. 171, 1035–1041 (2003).
  Article CAS PubMed Google Scholar
• Yang, C. H. et al. Interferon α/β promotes cell survival by activating nuclear factor κB through phosphatidylinositol 3-kinase and Akt. J. Biol. Chem. 276, 13756–13761 (2001).
  Article CAS PubMed Google Scholar
• Thyrell, L. et al. Interferon α-induced apoptosis in tumor cells is mediated through the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway. J. Biol. Chem. 279, 24152–24162 (2004).
  Article CAS PubMed Google Scholar
• Hwang, S. Y. et al. LY294002 inhibits interferon-γ-stimulated inducible nitric oxide synthase expression in BV2 microglial cells. Biochem. Biophys. Res. Commun. 318, 691–697 (2004).
  Article CAS PubMed Google Scholar
• Navarro, A., Anand-Apte, B., Tanabe, Y., Feldman, G. & Larner, A. C. A PI-3 kinase-dependent, Stat1-independent signaling pathway regulates interferon-stimulated monocyte adhesion. J. Leukoc. Biol. 73, 540–545 (2003).
  Article CAS PubMed Google Scholar
• Rani, M. R., Hibbert, L., Sizemore, N., Stark, G. R. & Ransohoff, R. M. Requirement of phosphoinositide 3-kinase and Akt for interferon-β-mediated induction of the _β_-R1 (SCYB11) gene. J. Biol. Chem. 277, 38456–38461 (2002).
  Article CAS PubMed Google Scholar
• Marcus, P. I. & Salb, J. M. Molecular basis of interferon action: inhibition of viral RNA translation. Virology 30, 502–516 (1966).
  Article CAS PubMed Google Scholar
• Doualla-Bell, F. & Koromilas, A. E. Induction of PG G/H synthase-2 in bovine myometrial cells by interferon-τ requires the activation of the p38 MAPK pathway. Endocrinology 142, 5107–5115 (2001).
  Article CAS PubMed Google Scholar
• Lekmine, F. et al. Activation of the p70 S6 kinase and phosphorylation of the 4E-BP1 repressor of mRNA translation by type I interferons. J. Biol. Chem. 278, 27772–27780 (2003). The first report that type I IFNs activate pathways for the initiation of mRNA translation that are downstream of MTOR.
  Article CAS PubMed Google Scholar
• Lekmine, F. et al. Interferon-γ engages the p70 S6 kinase to regulate phosphorylation of the 40S S6 ribosomal protein. Exp. Cell Res. 295, 173–182 (2004).
  Article CAS PubMed Google Scholar
• Hay, N. & Sonenberg, N. Upstream and downstream of mTOR. Genes Dev. 18, 1926–1945 (2004). A comprehensive review of MTOR and the regulation of signals for mRNA translation.
  Article CAS PubMed Google Scholar
• Bjornsti, M. A. & Houghton, P. J. The TOR pathway: a target for cancer therapy. Nature Rev. Cancer 4, 335–348 (2004).
  Article CAS Google Scholar
• Gingras, A. C. et al. Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev. 15, 2852–2864 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Lal, L. et al. Activation of the p70 S6 kinase by all-_trans_-retinoic acid in acute promyelocytic leukemia cells. Blood 105, 1669–1677 (2005).
  Article CAS PubMed Google Scholar
• Garber, K. Rapamycin's resurrection: a new way to target the cancer cell cycle. J. Natl Cancer Inst. 93, 1517–1519 (2001).
  Article CAS PubMed Google Scholar
• Ramana, C. V., Gil, P. M., Schreiber, R. D. & Stark, G. R. Stat1-dependent and -independent pathways in IFNγ-dependent signaling. Trends Immunol. 23, 96–101 (2002).
  Article CAS PubMed Google Scholar
• Sizemore, N. et al. Inhibitor of κB kinase is required to activate a subset of interferon γ-stimulated genes. Proc. Natl Acad. Sci. USA 101, 7994–7998 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Cantley, L. C. The phosphoinositide 3-kinase pathway. Science 296, 1655–1657 (2002).
  Article CAS PubMed Google Scholar
• Deane, J. A. & Fruman, D. A. Phosphoinositide 3-kinase: diverse roles in immune cell activation. Annu. Rev. Immunol. 22, 563–598 (2004).
  Article CAS PubMed Google Scholar
• Malik, A. H. & Lee, W. M. Chronic hepatitis B virus infection: treatment strategies for the next millennium. Ann. Intern. Med. 132, 723–731 (2000).
  Article CAS PubMed Google Scholar
• Liang, T. J., Rehermann, B., Seeff, L. B. & Hoofnagle, J. H. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann. Intern. Med. 132, 296–305 (2000).
  Article CAS PubMed Google Scholar
• Loutfy, M. R. et al. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. JAMA 290, 3222–3228 (2003).
  Article CAS PubMed Google Scholar