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Science 31 May 2002:
Vol. 296. no. 5573, pp. 1653 - 1655
DOI: 10.1126/science.1071545
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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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Interferon {gamma} Enhances the Effectiveness of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor Agonists in a Xenograft Model of Ewing's Sarcoma.
M. S. Merchant, X. Yang, F. Melchionda, M. Romero, R. Klein, C. J. Thiele, M. Tsokos, H. U. Kontny, and C. L. Mackall (2004)
Cancer Res. 64, 8349-8356
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Protein Kinase C{delta} Regulates Apoptosis via Activation of STAT1.
T. A. DeVries, R. L. Kalkofen, A. A. Matassa, and M. E. Reyland (2004)
J. Biol. Chem. 279, 45603-45612
   Abstract »    Full Text »    PDF »
Novel Aspects of Growth Hormone (GH) Autoregulation: GH-Induced GH Gene Expression in Grass Carp Pituitary Cells through Autocrine/Paracrine Mechanisms.
H. Zhou, W. K. W. Ko, W. K. K. Ho, S. S. Stojilkovic, and A. O. L. Wong (2004)
Endocrinology 145, 4615-4628
   Abstract »    Full Text »    PDF »
Engagement of Protein Kinase C-{theta} in Interferon Signaling in T-cells.
K. K. Srivastava, S. Batra, A. Sassano, Y. Li, B. Majchrzak, H. Kiyokawa, A. Altman, E. N. Fish, and L. C. Platanias (2004)
J. Biol. Chem. 279, 29911-29920
   Abstract »    Full Text »    PDF »
Characterization of the Amino Acid Residues of Sendai Virus C Protein That Are Critically Involved in Its Interferon Antagonism and RNA Synthesis Down-Regulation.
A. Kato, C. Cortese-Grogan, S. A. Moyer, F. Sugahara, T. Sakaguchi, T. Kubota, N. Otsuki, M. Kohase, M. Tashiro, and Y. Nagai (2004)
J. Virol. 78, 7443-7454
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Induction of Suppressor of Cytokine Signaling-3 by Herpes Simplex Virus Type 1 Contributes to Inhibition of the Interferon Signaling Pathway.
S.-i. Yokota, N. Yokosawa, T. Okabayashi, T. Suzutani, S. Miura, K. Jimbow, and N. Fujii (2004)
J. Virol. 78, 6282-6286
   Abstract »    Full Text »    PDF »
Angiotensin II Increases Pax-2 Expression in Fetal Kidney Cells Via the AT2 Receptor.
S.-L. Zhang, B. Moini, and J. R. Ingelfinger (2004)
J. Am. Soc. Nephrol. 15, 1452-1465
   Abstract »    Full Text »    PDF »
The Low Density Lipoprotein Receptor-related Protein Is a Motogenic Receptor for Plasminogen Activator Inhibitor-1.
B. Degryse, J. G. Neels, R.-P. Czekay, K. Aertgeerts, Y.-i. Kamikubo, and D. J. Loskutoff (2004)
J. Biol. Chem. 279, 22595-22604
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Identification of the Nuclear Export Signal and STAT-Binding Domains of the Nipah Virus V Protein Reveals Mechanisms Underlying Interferon Evasion.
J. J. Rodriguez, C. D. Cruz, and C. M. Horvath (2004)
J. Virol. 78, 5358-5367
   Abstract »    Full Text »    PDF »
Tyrosine 813 Is a Site of JAK2 Autophosphorylation Critical for Activation of JAK2 by SH2-B{beta}.
J. H. Kurzer, L. S. Argetsinger, Y.-J. Zhou, J.-L. K. Kouadio, J. J. O'Shea, and C. Carter-Su (2004)
Mol. Cell. Biol. 24, 4557-4570
   Abstract »    Full Text »    PDF »
Identification of Transcription Factor Binding Sites Upstream of Human Genes Regulated by the Phosphatidylinositol 3-Kinase and MEK/ERK Signaling Pathways.
J. W. Tullai, M. E. Schaffer, S. Mullenbrock, S. Kasif, and G. M. Cooper (2004)
J. Biol. Chem. 279, 20167-20177
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Identification of the Jak/Stat Proteins as Novel Downstream Targets of EphA4 Signaling in Muscle: IMPLICATIONS IN THE REGULATION OF ACETYLCHOLINESTERASE EXPRESSION.
K.-O. Lai, Y. Chen, H.-M. Po, K.-C. Lok, K. Gong, and N. Y. Ip (2004)
J. Biol. Chem. 279, 13383-13392
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Androgen Receptor Signaling: Mechanism of Interleukin-6 Inhibition.
L. Jia, C. S-Y. Choong, C. Ricciardelli, J. Kim, W. D. Tilley, and G. A Coetzee (2004)
Cancer Res. 64, 2619-2626
   Abstract »    Full Text »    PDF »
The JAK/STAT signaling pathway.
J. S. Rawlings, K. M. Rosler, and D. A. Harrison (2004)
J. Cell Sci. 117, 1281-1283
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Role of p38{alpha} Map Kinase in Type I Interferon Signaling.
Y. Li, A. Sassano, B. Majchrzak, D. K. Deb, D. E. Levy, M. Gaestel, A. R. Nebreda, E. N. Fish, and L. C. Platanias (2004)
J. Biol. Chem. 279, 970-979
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Survival Strategy of Obligately Intracellular Ehrlichia chaffeensis: Novel Modulation of Immune Response and Host Cell Cycles.
J.-z. Zhang, M. Sinha, B. A. Luxon, and X.-j. Yu (2004)
Infect. Immun. 72, 498-507
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Loss of dystrophin causes aberrant mechanotransduction in skeletal muscle fibers.
A. KUMAR, N. KHANDELWAL, R. MALYA, M. B. REID, and A. M. BORIEK (2004)
FASEB J 18, 102-113
   Abstract »    Full Text »    PDF »
Interferon-stimulated transcription and innate antiviral immunity require deacetylase activity and histone deacetylase 1.
I. Nusinzon and C. M. Horvath (2003)
PNAS 100, 14742-14747
   Abstract »    Full Text »    PDF »


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