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Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CIS, a cytokine inducible SH2 protein, is a target of the JAK-STAT5 pathway and modulates STAT5 activation A Matsumoto, M Masuhara, K Mitsui, M Yokouchi, M Ohtsubo, H Misawa, A Miyajima and A Yoshimura Insititute of Life Science, Kurume University, Japan. We searched for immediate early cytokine responsive genes and isolated a novel gene, CIS (Cytokine Inducible SH2 containing protein) that is induced in hematopoietic cells by a subset of cytokines including interleukin-2 (IL-2), IL-3, and erythropoietin (EPO). The mutant IL-2 receptor that fails to activate STAT5 could not induce CIS, suggesting that STAT5 is involved in the cytokine-inducible expression of CIS. We cloned the 5'-flanking region of the CIS gene and found that about 200 bases upstream of the transcription-initiation site contain four potential STAT5 binding sites (MGF boxes). Luciferase reporter assays showed that these MGF boxes were essential for EPO-dependent promoter activity. Expression of STAT5 and the EPO receptor in HEK293 cells conferred EPO-dependent activation of the CIS promoter. These data indicate that CIS is a target of the JAK-STAT5 pathway of cytokine receptors. CIS contains an SH2 domain and binds to tyrosine- phosphorylated EPO and IL-3 receptors. In HEK293 cells expressing STAT5 and the EPO receptor, EPO-dependent tyrosine phosphorylation of STAT5, as well as EPO-dependent CIS-promoter activation, was suppressed when CIS was coexpressed. Moreover, the induction of oncostatin M, another STAT5 target, as well as the tyrosine-phosphorylation of STAT5, were partially suppressed by CIS expression in Ba/F3 cells. Thus, CIS is a feedback modulator of STAT5; its expression is induced by STAT5 and it negatively modulates STAT5 activation. Volume 89, Issue 9, pp. 3148-3154, 05/01/1997 Copyright © 1997 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Piessevaux, L. De Ceuninck, D. Catteeuw, F. Peelman, and J. Tavernier Elongin B/C Recruitment Regulates Substrate Binding by CIS J. Biol. Chem., August 1, 2008; 283(31): 21334 - 21346. [Abstract] [Full Text] [PDF] J. Fang, M. Menon, D. Zhang, B. Torbett, L. Oxburgh, M. Tschan, E. Houde, and D. M. Wojchowski Attenuation of EPO-dependent erythroblast formation by death-associated protein kinase-2 Blood, August 1, 2008; 112(3): 886 - 890. [Abstract] [Full Text] [PDF] G. Kenth, J. A M. Mergelas, and C. G. Goodyer Developmental changes in the human GH receptor and its signal transduction pathways J. 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Migone, A. Sasaki, D. P. Ascherman, M.-h. Zhu, E. Soldaini, K. Imada, A. Miyajima, A. Yoshimura, and W. J. Leonard CIS Associates with the Interleukin-2 Receptor beta Chain and Inhibits Interleukin-2-dependent Signaling J. Biol. Chem., October 15, 1999; 274(42): 30266 - 30272. [Abstract] [Full Text] [PDF] M. L. Janas, P. Hodgkin, M. Hibbs, and D. Tarlinton Genetic Evidence for Lyn as a Negative Regulator of IL-4 Signaling J. Immunol., October 15, 1999; 163(8): 4192 - 4198. [Abstract] [Full Text] [PDF] M. A. Cassatella, S. Gasperini, C. Bovolenta, F. Calzetti, M. Vollebregt, P. Scapini, M. Marchi, R. Suzuki, A. Suzuki, and A. Yoshimura Interleukin-10 (IL-10) Selectively Enhances CIS3/SOCS3 mRNA Expression in Human Neutrophils: Evidence for an IL-10-Induced Pathway That Is Independent of STAT Protein Activation Blood, October 15, 1999; 94(8): 2880 - 2889. [Abstract] [Full Text] [PDF] S. A. Qureshi, R. M. Kim, Z. Konteatis, D. E. Biazzo, H. Motamedi, R. Rodrigues, J. A. Boice, J. R. Calaycay, M. A. Bednarek, P. Griffin, et al. Mimicry of erythropoietin by a nonpeptide molecule PNAS, October 12, 1999; 96(21): 12156 - 12161. [Abstract] [Full Text] [PDF] S. S. Watowich, X. Xie, U. Klingmuller, J. Kere, M. Lindlof, S. Berglund, and A. de la Chapelle Erythropoietin Receptor Mutations Associated With Familial Erythrocytosis Cause Hypersensitivity to Erythropoietin in the Heterozygous State Blood, October 1, 1999; 94(7): 2530 - 2532. [Abstract] [Full Text] [PDF] A. Matsumoto, Y. Seki, M. Kubo, S. Ohtsuka, A. Suzuki, I. Hayashi, K. Tsuji, T. Nakahata, M. Okabe, S. Yamada, et al. Suppression of STAT5 Functions in Liver, Mammary Glands, and T Cells in Cytokine-Inducible SH2-Containing Protein 1 Transgenic Mice Mol. Cell. Biol., September 1, 1999; 19(9): 6396 - 6407. [Abstract] [Full Text] [PDF] A. Pezet, H. Favre, P. A. Kelly, and M. Edery Inhibition and Restoration of Prolactin Signal Transduction by Suppressors of Cytokine Signaling J. Biol. 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A. Goldsmith Genetic Evidence for an Additional Factor Required for Erythropoietin-Induced Signal Transduction Blood, July 1, 1999; 94(1): 74 - 86. [Abstract] [Full Text] [PDF] C. J. Auernhammer, C. Bousquet, and S. Melmed Autoregulation of pituitary corticotroph SOCS-3 expression: Characterization of the murine SOCS-3 promoter PNAS, June 8, 1999; 96(12): 6964 - 6969. [Abstract] [Full Text] [PDF] C. Bjørbæk, J. K. Elmquist, K. El-Haschimi, J. Kelly, R. S. Ahima, S. Hileman, and J. S. Flier Activation of SOCS-3 Messenger Ribonucleic Acid in the Hypothalamus by Ciliary Neurotrophic Factor Endocrinology, May 1, 1999; 140(5): 2035 - 2043. [Abstract] [Full Text] M. Nieborowska-Skorska, M. A. Wasik, A. Slupianek, P. Salomoni, T. Kitamura, B. Calabretta, and T. Skorski Signal Transducer and Activator of Transcription (STAT)5 Activation by BCR/ABL Is Dependent on Intact Src Homology (SH)3 and SH2 Domains of BCR/ABL and Is Required for Leukemogenesis J. Exp. Med., April 19, 1999; 189(8): 1229 - 1242. [Abstract] [Full Text] [PDF] R. Y. Liu, C. Fan, R. Garcia, R. Jove, and K. S. Zuckerman Constitutive Activation of the JAK2/STAT5 Signal Transduction Pathway Correlates With Growth Factor Independence of Megakaryocytic Leukemic Cell Lines Blood, April 1, 1999; 93(7): 2369 - 2379. [Abstract] [Full Text] [PDF] C.G. Begley and N.A. Nicola Resolving Conflicting Signals: Cross Inhibition of Cytokine Signaling Pathways Blood, March 1, 1999; 93(5): 1443 - 1447. [Full Text] [PDF] S. Ito, P. Ansari, M. Sakatsume, H. Dickensheets, N. Vazquez, R. P. Donnelly, A. C. Larner, and D. S. Finbloom Interleukin-10 Inhibits Expression of Both Interferon alpha - and Interferon gamma - Induced Genes by Suppressing Tyrosine Phosphorylation of STAT1 Blood, March 1, 1999; 93(5): 1456 - 1463. [Abstract] [Full Text] [PDF] S. S. Watowich, K. D. Liu, X. Xie, S. Y. Lai, A. Mikami, G. D. Longmore, and M. A. Goldsmith Oligomerization and Scaffolding Functions of the Erythropoietin Receptor Cytoplasmic Tail J. Biol. Chem., February 26, 1999; 274(9): 5415 - 5421. [Abstract] [Full Text] [PDF] C. A. Gebert, S.-H. Park, and D. J. Waxman Down-Regulation of Liver JAK2-STAT5b Signaling by the Female Plasma Pattern of Continuous Growth Hormone Stimulation Mol. Endocrinol., February 1, 1999; 13(2): 213 - 227. [Abstract] [Full Text] A. Castro, T. K. Sengupta, D. C. Ruiz, E. Yang, and L. B. Ivashkiv IL-4 Selectively Inhibits IL-2-Triggered Stat5 Activation, But Not Proliferation, in Human T Cells J. Immunol., February 1, 1999; 162(3): 1261 - 1269. [Abstract] [Full Text] [PDF] C. A. Gebert, S.-H. Park, and D. J. Waxman Termination of Growth Hormone Pulse-Induced STAT5b Signaling Mol. Endocrinol., January 1, 1999; 13(1): 38 - 56. [Abstract] [Full Text]

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