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BRIEF REVIEWS |
Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38104
Universal and essential to cytokine receptor signaling, the JAK-STAT pathway is one of the best understood signal transduction cascades. Almost 40 cytokine receptors signal through combinations of four JAK and seven STAT family members, suggesting commonality across the JAK-STAT signaling system. Despite intense study, there remain substantial gaps in understanding how the cascades are activated and regulated. Using the examples of the IL-6 and IL-10 receptors, I will discuss how diverse outcomes in gene expression result from regulatory events that effect the JAK1-STAT3 pathway, common to both receptors. I also consider receptor preferences by different STATs and interpretive problems in the use of STAT-deficient cells and mice. Finally, I consider how the suppressor of cytokine signaling (SOCS) proteins regulate the quality and quantity of STAT signals from cytokine receptors. New data suggests that SOCS proteins introduce additional diversity into the JAK-STAT pathway by adjusting the output of activated STATs that alters downstream gene activation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the National Institutes of Health, Sandler Program for Asthma Research, Cancer Center Support CORE Grant P30 CA 21765, and the American Lebanese Syrian Associated Charities.
2 Address correspondence and reprint requests to Dr. Peter J. Murray, Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38104. E-mail address: peter.murray{at}stjude.org
3 Abbreviations used in this paper: SOCS, suppressor of cytokine signaling; EpoR, erythropoietin receptor.
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