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(Received for publication, November 27, 1995, and in revised form, February 28, 1996)
From the Department of Pulmonary Diseases, University Hospital
Utrecht, Utrecht, The Netherlands, and the The 89-kDa STAT3 protein is a latent
transcription factor which is activated in response to cytokines
(interleukin (IL)-5 and -6) and growth factors (epidermal growth
factor). Binding of IL-5 to its specific receptor activates JAK2 which
leads to the tyrosine phosphorylation of STAT3 proteins. Here we report
the cloning of a cDNA encoding a variant of the transcription
factor STAT3 (named STAT3
Volume 271, Number 21,
Issue of May 31, 1996
pp. 13221-13227
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
, a Splice Variant of Transcription Factor STAT3, Is a
Dominant Negative Regulator of Transcription
,
,
Glaxo Wellcome
Medicines Research Centre, Gunnels Wood Road, Stevenage,
Hertfordshire SG1 2NY, United Kingdom
) which was isolated by screening an
eosinophil cDNA library. Compared to wild-type STAT3, STAT3
lacks an internal domain of 50 base pairs located near the C terminus.
This splice product is a naturally occurring isoform of STAT3 and
encodes a 80-kDa protein. We found by reconstitution of the human IL-5R
in COS cells that like STAT3, STAT3 is phosphorylated on tyrosine
and binds to the pIRE from the ICAM-1 promoter after IL-5 stimulation.
However, STAT3 fails to activate a pIRE containing promoter in
transient transfection assays. Instead, co-expression of STAT3
inhibits the transactivation potential of STAT3. These results suggests
that STAT3 functions as a negative regulator of transcription.
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A. Chakraborty, K. F. Dyer, M. Cascio, T. A. Mietzner, and D. J. Tweardy Identification of a Novel Stat3 Recruitment and Activation Motif Within the Granulocyte Colony-Stimulating Factor Receptor Blood, January 1, 1999; 93(1): 15 - 24. [Abstract] [Full Text] [PDF]
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T. B. van Dijk, B. Baltus, E. Caldenhoven, H. Handa, J. A.M. Raaijmakers, J.-W. J. Lammers, L. Koenderman, and R. P. de Groot Cloning and Characterization of the Human Interleukin-3 (IL-3)/IL-5/ Granulocyte-Macrophage Colony-Stimulating Factor Receptor beta c Gene: Regulation by Ets Family Members Blood, November 15, 1998; 92(10): 3636 - 3646. [Abstract] [Full Text] [PDF]
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J. Turkson, T. Bowman, R. Garcia, E. Caldenhoven, R. P. De Groot, and R. Jove Stat3 Activation by Src Induces Specific Gene Regulation and Is Required for Cell Transformation Mol. Cell. Biol., May 1, 1998; 18(5): 2545 - 2552. [Abstract] [Full Text]
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K. Inoue, H. Tamaki, H. Ogawa, Y. Oka, T. Soma, T. Tatekawa, Y. Oji, A. Tsuboi, E. H. Kim, M. Kawakami, et al. Wilms' Tumor Gene (WT1) Competes With Differentiation-Inducing Signal in Hematopoietic Progenitor Cells Blood, April 15, 1998; 91(8): 2969 - 2976. [Abstract] [Full Text] [PDF]
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T. B. van Dijk, E. Caldenhoven, J. A.M. Raaijmakers, J.-W. J. Lammers, L. Koenderman, and R. P. de Groot The Role of Transcription Factor PU.I in the Activity of the Intronic Enhancer of the Eosinophil-Derived Neurotoxin (RNS2) Gene Blood, March 15, 1998; 91(6): 2126 - 2132. [Abstract] [Full Text] [PDF]
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B. K. R. Patel, J. H. Pierce, and W. J. LaRochelle Regulation of interleukin 4-mediated signaling by naturally occurring dominant negative and attenuated forms of human Stat6 PNAS, January 6, 1998; 95(1): 172 - 177. [Abstract] [Full Text] [PDF]
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S. Takemoto, J. C. Mulloy, A. Cereseto, T.-S. Migone, B. K. R. Patel, M. Matsuoka, K. Yamaguchi, K. Takatsuki, S. Kamihira, J. D. White, et al. Proliferation of adult T cell leukemia/lymphoma cells is associated with the constitutive activation of JAK/STAT proteins PNAS, December 9, 1997; 94(25): 13897 - 13902. [Abstract] [Full Text] [PDF]
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M. J. Walter, D. C. Look, R. M. Tidwell, W. T. Roswit, and M. J. Holtzman Targeted Inhibition of Interferon-gamma -dependent Intercellular Adhesion Molecule-1 (ICAM-1) Expression Using Dominant-Negative Stat1 J. Biol. Chem., November 7, 1997; 272(45): 28582 - 28589. [Abstract] [Full Text] [PDF]
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J. Ng and D. Cantrell STAT3 Is a Serine Kinase Target in T Lymphocytes. INTERLEUKIN 2 AND T CELL ANTIGEN RECEPTOR SIGNALS CONVERGE UPON SERINE 727 J. Biol. Chem., September 26, 1997; 272(39): 24542 - 24549. [Abstract] [Full Text] [PDF]
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M. Nielsen, K. Kaltoft, M. Nordahl, C. Ropke, C. Geisler, T. Mustelin, P. Dobson, A. Svejgaard, and N. Odum Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: Tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell lines PNAS, June 24, 1997; 94(13): 6764 - 6769. [Abstract] [Full Text] [PDF]
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K. K. Kuropatwinski, C. De Imus, D. Gearing, H. Baumann, and B. Mosley Influence of Subunit Combinations on Signaling by Receptors for Oncostatin M, Leukemia Inhibitory Factor, and Interleukin-6 J. Biol. Chem., June 13, 1997; 272(24): 15135 - 15144. [Abstract] [Full Text] [PDF]
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H. Kim and H. Baumann The Carboxyl-terminal Region of STAT3 Controls Gene Induction by the Mouse Haptoglobin Promoter J. Biol. Chem., June 6, 1997; 272(23): 14571 - 14579. [Abstract] [Full Text] [PDF]
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R. A. Kirken, M. G. Malabarba, J. Xu, X. Liu, W. L. Farrar, L. Hennighausen, A. C. Larner, P. M. Grimley, and H. Rui Prolactin Stimulates Serine/Tyrosine Phosphorylation and Formation of Heterocomplexes of Multiple Stat5 Isoforms in Nb2 Lymphocytes J. Biol. Chem., May 30, 1997; 272(22): 14098 - 14103. [Abstract] [Full Text] [PDF]
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R. P. de Groot, T. B. van Dijk, E. Caldenhoven, P. J. Coffer, J. A.M. Raaijmakers, J.-W. J. Lammers, and L. Koenderman Activation of 12-O-Tetradecanoylphorbol-13-acetate Response Element- and Dyad Symmetry Element-dependent Transcription by Interleukin-5 Is Mediated by Jun N-terminal Kinase/Stress-activated Protein Kinase Kinases J. Biol. Chem., January 24, 1997; 272(4): 2319 - 2325. [Abstract] [Full Text] [PDF]
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Y. Zhang, J. Turkson, C. Carter-Su, T. Smithgall, A. Levitzki, A. Kraker, J. J. Krolewski, P. Medveczky, and R. Jove Activation of Stat3 in v-Src-transformed Fibroblasts Requires Cooperation of Jak1 Kinase Activity J. Biol. Chem., August 4, 2000; 275(32): 24935 - 24944. [Abstract] [Full Text] [PDF]
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O. K. Park, L. K. Schaefer, W. Wang, and T. S. Schaefer Dimer Stability as a Determinant of Differential DNA Binding Activity of Stat3 Isoforms J. Biol. Chem., October 6, 2000; 275(41): 32244 - 32249. [Abstract] [Full Text] [PDF]
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T. Bowman, M. A. Broome, D. Sinibaldi, W. Wharton, W. J. Pledger, J. M. Sedivy, R. Irby, T. Yeatman, S. A. Courtneidge, and R. Jove Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis PNAS, June 19, 2001; 98(13): 7319 - 7324. [Abstract] [Full Text] [PDF]
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T. R. Faruqi, D. Gomez, X. R. Bustelo, D. Bar-Sagi, and N. C. Reich Rac1 mediates STAT3 activation by autocrine IL-6 PNAS, July 31, 2001; 98(16): 9014 - 9019. [Abstract] [Full Text] [PDF]
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