Uncoupling of proliferation and Stat5 activation in thymic stromal lymphopoietin-mediated signal transduction

Deborah E. Isaksen, Heinz Baumann, Baohua Zhou, Sebastien Nivollet, Andrew G. Farr, Steven D. Levin, Steven F. Ziegler

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Thymic stromal lymphopoietin (TSLP) is a cytokine that facilitates B lymphocyte differentiation and costimulates T cells. Previous studies have demonstrated that a functional TSLP receptor complex is a heterodimer consisting of the TSLP receptor and the IL-7R α-chain. TSLP-mediated signaling is unique among members of the cytokine receptor family in that activation of the transcription factor Stat5 occurs without detectable Janus kinase activation. Using a variety of biological systems we demonstrate here that TSLP-mediated Stat5 activation can be uncoupled from proliferation. We also show that the single tyrosine residue in the cytoplasmic domain of the TSLP receptor is critical for TSLP-mediated proliferation, but is dispensable for Stat5 activation. Our data demonstrate that TSLP-mediated Stat5 activation is insufficient for cell proliferation and identifies residues within the TSLP receptor complex required to mediate these downstream events.

Original languageEnglish (US)
Pages (from-to)3288-3294
Number of pages7
JournalJournal of Immunology
Volume168
Issue number7
DOIs
StatePublished - Apr 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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