Regulation of cytokine signaling

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

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationCell Signaling in Vascular Inflammation
PublisherHumana Press
Pages103-111
Number of pages9
ISBN (Print)1588295257, 9781588295255
DOIs
StatePublished - Dec 1 2005

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Vuong, B. Q., McKeag, L., Losman, J. A., Li, J., Banks, A., Fay, S., Chen, P., & Rothman, P. (2005). Regulation of cytokine signaling. In Cell Signaling in Vascular Inflammation (pp. 103-111). Humana Press. https://doi.org/10.1007/978-1-59259-909-7_11