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 alpha-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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution / genetics
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Animals
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Cell Division / genetics
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Cell Division / immunology
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Cell Line
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Cytokines / antagonists & inhibitors
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Cytokines / metabolism
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Cytokines / physiology*
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Cytoplasm / genetics
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Cytoplasm / physiology
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DNA-Binding Proteins / metabolism*
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DNA-Binding Proteins / physiology
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Humans
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Interleukin-7 / metabolism
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Interleukin-7 / physiology*
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Lymphocyte Activation* / genetics
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Mice
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Milk Proteins*
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Protein Structure, Tertiary / genetics
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Protein Structure, Tertiary / physiology
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Receptors, Interleukin-7 / genetics
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Receptors, Interleukin-7 / physiology
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STAT5 Transcription Factor
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Stromal Cells / physiology
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Thymic Stromal Lymphopoietin
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Thymus Gland / physiology*
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Trans-Activators / metabolism*
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Trans-Activators / physiology
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Tumor Cells, Cultured
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Tyrosine / genetics
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Tyrosine / physiology
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src-Family Kinases / antagonists & inhibitors
Substances
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Cytokines
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DNA-Binding Proteins
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Interleukin-7
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Milk Proteins
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Receptors, Interleukin-7
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STAT5 Transcription Factor
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Trans-Activators
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Tyrosine
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src-Family Kinases
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Thymic Stromal Lymphopoietin