Evidence for the Involvement of JAK/STAT Pathway in the Signaling Mechanism of Interleukin-17

Interleukin-17 is a T-cell-derived pro-inflammatory cytokine, exhibiting multiple biological activities in a variety of cells and believed to fine tune all general phases of hematopoietic response. However, the signaling mechanism of this novel cytokine remains unknown. Here, we report for the first...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1999-08, Vol.262 (1), p.14-19
Main Authors: Subramaniam, S.Vaidyanathan, Cooper, Roland S., Adunyah, Samuel E.
Format: Article
Language:English
Subjects:
Blotting, Western
DNA-Binding Proteins - metabolism
Humans
Interleukin-17 - pharmacology
Janus Kinase 1
Janus Kinase 2
Janus Kinase 3
Phosphorylation - drug effects
Phosphotyrosine - metabolism
Precipitin Tests
Protein-Tyrosine Kinases - metabolism
Proteins - metabolism
Proto-Oncogene Proteins
Receptors, Interleukin - analysis
Receptors, Interleukin-17
Recombinant Proteins - analysis
Signal Transduction - drug effects
STAT1 Transcription Factor
STAT2 Transcription Factor
STAT3 Transcription Factor
STAT4 Transcription Factor
Time Factors
Trans-Activators - metabolism
TYK2 Kinase
U937 Cells
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Summary:Interleukin-17 is a T-cell-derived pro-inflammatory cytokine, exhibiting multiple biological activities in a variety of cells and believed to fine tune all general phases of hematopoietic response. However, the signaling mechanism of this novel cytokine remains unknown. Here, we report for the first time that the early signaling events triggered by interleukin-17 involve tyrosine phosphorylation of several members of the JAK and STAT proteins in human U937 monocytic leukemia cells. Immunoprecipitation with specific antibodies followed by Western blot analysis with antiphosphotyrosine antibody has shown that in U937 cells, interleukin-17 induces time-dependent stimulation of tyrosine phosphorylation of JAK 1, 2 and 3, Tyk 2 and STAT 1, 2, 3 and 4 within 0.5 to 30 min. Interleukin-17-mediated tyrosine phosphorylation of these proteins strongly suggests that the JAK/STAT signaling pathway may play a major role in transducing signals from interleukin-17 receptors to the nucleus.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.1156