The Src-protein tyrosine kinase Lck is required for IL-1-mediated costimulatory signaling in Th2 cells

B. K. Al-Ramadi, T. Welte, M. J. Fernandez-Cabezudo, S. Galadari, B. Dittel, X. Y. Fu, A. L.M. Bothwell

Research output: Contribution to journalArticle

Abstract

Src-protein tyrosine kinases are intimately involved in TCR-initiated signaling in T lymphocytes. One member of this family, Lck, is also involved in CD28-mediated costimulation in Th1 cells. In Th2 lymphocytes, the costimulatory signal can also be provided by the interaction of IL-1 with type I IL-1R (IL-1RI), culminating in the activation of NF-κB transcription factors. Proximal steps in the IL-1R pathway, however, remain poorly understood, and there is conflicting evidence as to the importance of tyrosine phosphorylation in IL-1R signaling. We have addressed this issue by examining the ability of IL-1 to costimulate the activation of Lck-deficient Th2 cells. Our data demonstrate that, in the absence of Lck, the IL-1 costimulatory pathway is blocked despite the expression of normal levels of IL-1RI. Moreover, the block is associated with a defective degradation of IκB-α and an incomplete activation of NF-κB heterodimeric complexes. Protein expression of NF-κB monomers, including p50, p65, and c-Rel, is equivalent in both wild-type and Lck-deficient Th2 cell clones. Finally, we demonstrate that, in normal Th2 cells, stimulation with IL-1 leads to a rapid induction in tyrosine phosphorylation of several substrates including Lck itself. These findings strongly suggest that Lck is required for signaling in the IL-1 costimulatory pathway in Th2 lymphocytes.

Original languageEnglish (US)
Pages (from-to)6827-6833
Number of pages7
JournalJournal of Immunology
Volume167
Issue number12
DOIs
StatePublished - Dec 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Al-Ramadi, B. K., Welte, T., Fernandez-Cabezudo, M. J., Galadari, S., Dittel, B., Fu, X. Y., & Bothwell, A. L. M. (2001). The Src-protein tyrosine kinase Lck is required for IL-1-mediated costimulatory signaling in Th2 cells. Journal of Immunology, 167(12), 6827-6833. https://doi.org/10.4049/jimmunol.167.12.6827