Interleukin 2 signaling involves the phosphorylation of Stat proteins

David A. Frank, Michael J. Robertson, Azad Bonni, Jerome Ritz, Michael E. Greenberg

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

One of the most important cytokines involved in immune response regulation is interleukin 2 (IL-2), a potent activator of the proliferation and function of T lymphocytes and natural killer cells. The mechanisms by which the effects of IL-2 are propagated within cells are not understood. While the binding of IL-2 to its receptor was recently shown to lead to the activation of two kinases, Jak-1 and Jak-3, subsequent steps in the signaling pathway to the nucleus that lead to the activation of specific genes had not been characterized. Since many cytokines that activate Jak kinases also lead to the tyrosine phosphorylation and activation of members of the Stat family of transcription factors, the ability of IL-2 to trigger Stat phosphorylation was examined. Exposure of activated human T lymphocytes or of a natural killer cell line (NKL) to IL-2 leads to the phosphorylation of Stat1α, Stat1β, and Stat3, as well as of two Stat-related proteins, p94 and p95, p94 and p95 share homology with Stat1 at the phosphorylation site and in the Src homology 2 (SH2) domain, but otherwise are immunologically distinct from Stat1. These Stat proteins were found to translocate to the nucleus and to bind to a specific DNA sequence. These findings suggest a mechanism by which IL-2 binding to its receptor may activate specific genes involved in immune cell function.

Original languageEnglish
Pages (from-to)7779-7783
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number17
DOIs
StatePublished - Aug 15 1995

Keywords

  • cytokine
  • lymphocyte
  • natural killer cell
  • tyrosine phosphorylation

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