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Cell Signaling in Vascular Inflammation pp 103–111Cite as

Regulation of Cytokine Signaling

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Abstract

Cytokines are important modulators of the immune response that underlies the inflammatory process in atopic forms of asthma. Interleukin (IL)-4 and IL-13 are important cytokines for the regulation of these asthmatic immune responses. However, the cellular mechanisms that regulate IL-4 and IL-13 signaling remain unknown. Recently, a new family of proteins, termed suppressors of cytokine signaling (SOCS), has been identified. We have previously shown that SOCS-1 is a potent inhibitor of JAK-STAT signaling activated by IL-4. SOCS-1 expression is regulated both at the RNA and protein stability level. To identify proteins that bind and potentially regulate SOCS-1, we used the yeast two-hybrid system. We have identified the serine-threonine kinase Pim-2 as a binding partner for SOCS-1. Our preliminary studies demonstrate that SOCS-1 can interact with all three Pim kinases in mammalian cells. Co-expression of SOCS-1 with Pim kinases leads to the expression of novel SOCS-1 isoforms to require serine-threonine kinase activity. Pim kinases can directly phosphorylate SOCS-1. In addition, co-expression of SOCS-1 with Pim2 increases the levels of SOCS-1 protein. Finally, expression of Pim-2 increases the inhibition of IL-4 signaling by SOCS-1. These data lead to a model by which the expression of Pim kinases alters SOCS-1 function through a phosphorylation event that stabilizes the SOCS-1 protein. This chapter proposes experiments to test this model and determine the role Pim kinases play in regulating IL-4 signaling in vivo. In addition, we propose to study the role of Pim kinases in a murine model of asthma.

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Authors and Affiliations

  1. Departments of Medicine and Microbiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA

    Bao Q. Vuong, Lisa McKeag, Julie A. Losman, Jianze Li, Alex Banks, Scott Fay, Peter Chen & Paul Rothman Md

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  1. Bao Q. Vuong
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Editors and Affiliations

  1. Clinical Physiological Medicine, and Medicine, Columbia University, New York, NY, USA

    Jahar Bhattacharya MBBS, DPhil (Professor of Physiology and Cellular Biophysics) (Professor of Physiology and Cellular Biophysics)

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© 2005 Humana Press Inc., Totowa, NJ

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Vuong, B.Q. et al. (2005). Regulation of Cytokine Signaling. In: Bhattacharya, J. (eds) Cell Signaling in Vascular Inflammation. Humana Press. https://doi.org/10.1007/978-1-59259-909-7_11

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  • DOI: https://doi.org/10.1007/978-1-59259-909-7_11

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-525-5

  • Online ISBN: 978-1-59259-909-7

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