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Science 296 (5573): 1653-1655

Copyright © 2002 by the American Association for the Advancement of Science

A Road Map for Those Who Don't Know JAK-STAT

David S. Aaronson,1 Curt M. Horvath2*

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway transmits information received from extracellular polypeptide signals, through transmembrane receptors, directly to target gene promoters in the nucleus, providing a mechanism for transcriptional regulation without second messengers. Evolutionarily conserved in eukaryotic organisms from slime molds to humans, JAK-STAT signaling appears to be an early adaptation to facilitate intercellular communication that has co-evolved with myriad cellular signaling events. This co-evolution has given rise to highly adapted, ligand-specific signaling pathways that control gene expression. In addition, the JAK-STAT signaling pathways are regulated by a vast array of intrinsic and environmental stimuli, which can add plasticity to the response of a cell or tissue.

1 Department of Pharmacology and Biological Chemistry,
2 Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029 USA.
*   To whom correspondence should be addressed. E-mail: curt.horvath{at}mssm.edu



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M. J. Trifilo, B. Hahm, E. I. Zuniga, K. H. Edelmann, and M. B. A. Oldstone (2006)
The Journal of Infectious Disease 194, S3-S10
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Haplotype of Signal Transducer and Activator of Transcription 3 Gene Predicts Cardiovascular Disease in Dialysis Patients.
L. Zhang, W.H. L. Kao, Y. Berthier-Schaad, Y. Liu, L. Plantinga, B. G. Jaar, N. Fink, N. Powe, M. J. Klag, M. W. Smith, et al. (2006)
J. Am. Soc. Nephrol. 17, 2285-2292
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Arginine-Vasopressin Activates the JAK-STAT Pathway in Vascular Smooth Muscle Cells.
O. Levy and Y. Granot (2006)
J. Biol. Chem. 281, 15597-15604
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UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity.
O. A. Malakhova, K. I. Kim, J.-K. Luo, W. Zou, K. S. Kumar, S. Y. Fuchs, K. Shuai, and D.-E. Zhang (2006)
EMBO J. 25, 2358-2367
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Cytokine-induced metabolic effects in human adipocytes are independent of endogenous nitric oxide.
P. Linscheid, D. Seboek, H. Zulewski, A. Scherberich, N. Blau, U. Keller, and B. Muller (2006)
Am J Physiol Endocrinol Metab 290, E1068-E1077
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Tid1 Isoforms Are Mitochondrial DnaJ-like Chaperones with Unique Carboxyl Termini That Determine Cytosolic Fate.
B. Lu, N. Garrido, J. N. Spelbrink, and C. K. Suzuki (2006)
J. Biol. Chem. 281, 13150-13158
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Inhibition of Interferon Signaling by Rabies Virus Phosphoprotein P: Activation-Dependent Binding of STAT1 and STAT2.
K. Brzozka, S. Finke, and K.-K. Conzelmann (2006)
J. Virol. 80, 2675-2683
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A human cytomegalovirus antagonist of type I IFN-dependent signal transducer and activator of transcription signaling.
C. Paulus, S. Krauss, and M. Nevels (2006)
PNAS 103, 3840-3845
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Pathways of matrix metalloproteinase induction in heart failure: Bioactive molecules and transcriptional regulation.
A. M. Deschamps and F. G. Spinale (2006)
Cardiovasc Res 69, 666-676
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Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in response to interleukin-6 receptor and epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas.
T. L. Lee, J. Yeh, C. Van Waes, and Z. Chen (2006)
Mol. Cancer Ther. 5, 8-19
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Flavopiridol disrupts STAT3/DNA interactions, attenuates STAT3-directed transcription, and combines with the Jak kinase inhibitor AG490 to achieve cytotoxic synergy.
Y. K. Lee, C. R. Isham, S. H. Kaufman, and K. C. Bible (2006)
Mol. Cancer Ther. 5, 138-148
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A Distal Regulatory Region Is Required for Constitutive and IFN-{beta}-Induced Expression of Murine TLR9 Gene.
Z. Guo, S. Garg, K. M. Hill, L. Jayashankar, M. R. Mooney, M. Hoelscher, J. M. Katz, J. M. Boss, and S. Sambhara (2005)
J. Immunol. 175, 7407-7418
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Rabies Virus P Protein Interacts with STAT1 and Inhibits Interferon Signal Transduction Pathways.
A. Vidy, M. Chelbi-Alix, and D. Blondel (2005)
J. Virol. 79, 14411-14420
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Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2.
R. Kralovics, S.-S. Teo, A. S. Buser, M. Brutsche, R. Tiedt, A. Tichelli, F. Passamonti, D. Pietra, M. Cazzola, and R. C. Skoda (2005)
Blood 106, 3374-3376
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Treatment of Autoimmune Neuroinflammation with a Synthetic Tryptophan Metabolite.
M. Platten, P. P. Ho, S. Youssef, P. Fontoura, H. Garren, E. M. Hur, R. Gupta, L. Y. Lee, B. A. Kidd, W. H. Robinson, et al. (2005)
Science 310, 850-855
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Cyclooxygenase-2-Dependent Activation of Signal Transducer and Activator of Transcription 3 by Interleukin-6 in Non-Small Cell Lung Cancer.
H. Dalwadi, K. Krysan, N. Heuze-Vourc'h, M. Dohadwala, D. Elashoff, S. Sharma, N. Cacalano, A. Lichtenstein, and S. Dubinett (2005)
Clin. Cancer Res. 11, 7674-7682
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Apical role for BRG1 in cytokine-induced promoter assembly.
Z. Ni, E. Karaskov, T. Yu, S. M. Callaghan, S. Der, D. S. Park, Z. Xu, S. G. Pattenden, and R. Bremner (2005)
PNAS 102, 14611-14616
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Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System.
Z. W. Wang, L. Sarmento, Y. Wang, X.-q. Li, V. Dhingra, T. Tseggai, B. Jiang, and Z. F. Fu (2005)
J. Virol. 79, 12554-12565
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