Regulation of Cytokine Signaling

  • Bao Q. Vuong
  • Lisa McKeag
  • Julie A. Losman
  • Jianze Li
  • Alex Banks
  • Scott Fay
  • Peter Chen
  • Paul Rothman
Chapter

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.

Key Words

PIM kinases SOCS (suppressor of cytokine signaling) interleukin-4 (IL-4) interferon-γ (IFN-γ) cytokine signaling allergy 
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Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Bao Q. Vuong
    • 1
  • Lisa McKeag
    • 1
  • Julie A. Losman
    • 1
  • Jianze Li
    • 1
  • Alex Banks
    • 1
  • Scott Fay
    • 1
  • Peter Chen
    • 1
  • Paul Rothman
    • 1
  1. 1.Departments of Medicine and MicrobiologyCollege of Physicians and Surgeons of Columbia UniversityNew YorkUSA

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