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Science 12 September 1997:
Vol. 277. no. 5332, pp. 1630 - 1635
DOI: 10.1126/science.277.5332.1630
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Articles

STATs and Gene Regulation

James E. Darnell Jr.

STATs (signal transducers and activators of transcription) are a family of latent cytoplasmic proteins that are activated to participate in gene control when cells encounter various extracellular polypeptides. Biochemical and molecular genetic explorations have defined a single tyrosine phosphorylation site and, in a dimeric partner molecule, an Src homology 2 (SH2) phosphotyrosine-binding domain, a DNA interaction domain, and a number of protein-protein interaction domains (with receptors, other transcription factors, the transcription machinery, and perhaps a tyrosine phosphatase). Mouse genetics experiments have defined crucial roles for each known mammalian STAT. The discovery of a STAT in Drosophila, and most recently in Dictyostelium discoideum, implies an ancient evolutionary origin for this dual-function set of proteins.

The author is in the Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021, USA.

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Y. Matsuzaki, V. Besnard, J. C. Clark, Y. Xu, S. E. Wert, M. Ikegami, and J. A. Whitsett (2008)
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D. A Frank (2008)
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M. C. Simeone-Penney, M. Severgnini, L. Rozo, S. Takahashi, B. H. Cochran, and A. R. Simon (2008)
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T. Nagashima, T. Maruyama, H. Uchida, T. Kajitani, T. Arase, M. Ono, H. Oda, M. Kagami, H. Masuda, S. Nishikawa, et al. (2008)
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BART is essential for nuclear retention of STAT3.
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Y. Wang, D. Liu, P. Chen, H. P. Koeffler, X. Tong, and D. Xie (2008)
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K. Boengler, A. Buechert, Y. Heinen, C. Roeskes, D. Hilfiker-Kleiner, G. Heusch, and R. Schulz (2008)
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S. Choi and J.N. Myers (2008)
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Endocrinology 148, 6073-6082
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STAT3 Polymorphism Predicts Interferon-Alfa Response in Patients With Metastatic Renal Cell Carcinoma.
N. Ito, M. Eto, E. Nakamura, A. Takahashi, T. Tsukamoto, H. Toma, H. Nakazawa, Y. Hirao, H. Uemura, S. Kagawa, et al. (2007)
J. Clin. Oncol. 25, 2785-2791
   Abstract »    Full Text »    PDF »
Olanzapine Increases RGS7 Protein Expression via Stimulation of the Janus Tyrosine Kinase-Signal Transducer and Activator of Transcription Signaling Cascade.
R. K. Singh, J. Shi, B. W. Zemaitaitis, and N. A. Muma (2007)
J. Pharmacol. Exp. Ther. 322, 133-140
   Abstract »    Full Text »    PDF »
Integration of Steroid and Growth Factor Pathways in Breast Cancer: Focus on Signal Transducers and Activators of Transcription and Their Potential Role in Resistance.
C. M. Silva and M. A. Shupnik (2007)
Mol. Endocrinol. 21, 1499-1512
   Abstract »    Full Text »    PDF »
Characterization of Three Growth Hormone-Responsive Transcription Factors Preferentially Expressed in Adult Female Liver.
E. V. Laz, M. G. Holloway, C.-S. Chen, and D. J. Waxman (2007)
Endocrinology 148, 3327-3337
   Abstract »    Full Text »    PDF »
Growth Hormone Stimulates Hepatic Expression of Bovine Growth Hormone Receptor Messenger Ribonucleic Acid through Signal Transducer and Activator of Transcription 5 Activation of a Major Growth Hormone Receptor Gene Promoter.
H. Jiang, Y. Wang, M. Wu, Z. Gu, S. J. Frank, and R. Torres-Diaz (2007)
Endocrinology 148, 3307-3315
   Abstract »    Full Text »    PDF »
Ubp43 regulates BCR-ABL leukemogenesis via the type 1 interferon receptor signaling.
M. Yan, J.-K. Luo, K. J. Ritchie, I. Sakai, K. Takeuchi, R. Ren, and D.-E. Zhang (2007)
Blood 110, 305-312
   Abstract »    Full Text »    PDF »
MUC1 Oncoprotein Promotes Refractoriness to Chemotherapy in Thyroid Cancer Cells.
M. Siragusa, M. Zerilli, F. Iovino, M. G. Francipane, Y. Lombardo, L. Ricci-Vitiani, G. Di Gesu, M. Todaro, R. De Maria, and G. Stassi (2007)
Cancer Res. 67, 5522-5530
   Abstract »    Full Text »    PDF »
Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine model of asthma via regulatory T cells.
S. Finotto, T. Eigenbrod, R. Karwot, I. Boross, A. Doganci, H. Ito, N. Nishimoto, K. Yoshizaki, T. Kishimoto, S. Rose-John, et al. (2007)
Int. Immunol. 19, 685-693
   Abstract »    Full Text »    PDF »
Evidence that Noncoding RNA dutA Is a Multicopy Suppressor of Dictyostelium discoideum STAT Protein Dd-STATa.
N. Shimada and T. Kawata (2007)
Eukaryot. Cell 6, 1030-1040
   Abstract »    Full Text »    PDF »
Airway Epithelial STAT3 Is Required for Allergic Inflammation in a Murine Model of Asthma.
M. C. Simeone-Penney, M. Severgnini, P. Tu, R. J. Homer, T. J. Mariani, L. Cohn, and A. R. Simon (2007)
J. Immunol. 178, 6191-6199
   Abstract »    Full Text »    PDF »
Leptin-induced Growth Stimulation of Breast Cancer Cells Involves Recruitment of Histone Acetyltransferases and Mediator Complex to CYCLIN D1 Promoter via Activation of Stat3.
N. K. Saxena, P. M. Vertino, F. A. Anania, and D. Sharma (2007)
J. Biol. Chem. 282, 13316-13325
   Abstract »    Full Text »    PDF »
Loss of Sexually Dimorphic Liver Gene Expression upon Hepatocyte-Specific Deletion of Stat5a-Stat5b Locus.
M. G. Holloway, Y. Cui, E. V. Laz, A. Hosui, L. Hennighausen, and D. J. Waxman (2007)
Endocrinology 148, 1977-1986
   Abstract »    Full Text »    PDF »
STAT3 signaling is activated in human skeletal muscle following acute resistance exercise.
M. K. Trenerry, K. A. Carey, A. C. Ward, and D. Cameron-Smith (2007)
J Appl Physiol 102, 1483-1489
   Abstract »    Full Text »    PDF »
Cell Confluence-induced Activation of Signal Transducer and Activator of Transcription-3 (Stat3) Triggers Epithelial Dome Formation via Augmentation of Sodium Hydrogen Exchanger-3 (NHE3) Expression.
H.-W. Su, H.-H. Yeh, S.-W. Wang, M.-R. Shen, T.-L. Chen, P. R. Kiela, F. K. Ghishan, and M.-J. Tang (2007)
J. Biol. Chem. 282, 9883-9894
   Abstract »    Full Text »    PDF »
Antiviral and immunoregulatory activities of IFN-{gamma} depend on constitutively expressed IL-1{alpha}.
V. Hurgin, D. Novick, A. Werman, C. A. Dinarello, and M. Rubinstein (2007)
PNAS 104, 5044-5049
   Abstract »    Full Text »    PDF »


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