DOI: 10.4049/jimmunol.160.6.2742. Induction of Jak/STAT Signaling by Activation of the Type 1 TNF Receptor

Induction of Jak/STAT Signaling by Activation of the Type 1 TNF Receptor
10.4049/jimmunol.160.6.2742
Crossref journal-article
Oxford University Press (OUP)
The Journal of Immunology (286)
Abstract
AbstractCellular responses to TNF are initiated by either of two cell surface receptors, the type 1 TNF receptor (TNFR1) and the type 2 TNF receptor (TNFR2). Although neither receptor contains an intrinsic protein tyrosine kinase, such activity has been implicated in TNF action. In this study, we show that murine TNF induces the tyrosine phosphorylation and activation of the intracellular Janus tyrosine kinases Jak1, Jak2, and Tyk2 in murine 3T3-L1 adipocytes. Activation of Jak kinases by TNF was associated with tyrosine phosphorylation of STAT1, STAT3, STAT5, and STAT6, but not STAT2 or STAT4, showing that TNF acts on a specific subset of these latent cytoplasmic transcription factors in 3T3-L1 adipocytes. Agonist antiserum to TNFR1 induced Jak kinase and STAT protein phosphorylation. Phosphorylation of Jak proteins was also induced by human TNF, which selectively binds to TNFR1 on murine cells. 35S-labeled Jak kinases were precipitated from a cell-free system and from lysates of 3T3-L1 adipocytes by a glutathione S-transferase fusion protein containing the cytoplasmic domain of TNFR1. These results suggest that the cytoplasmic domain of TNFR1 can directly interact with and form signaling complexes with Jak kinases. Jak2 was precipitated from HeLa cells by antiserum to TNFR1, directly demonstrating their association in vivo. Thus, TNF activates a Jak/STAT signal-transduction cascade by acting through TNFR1.
Bibliography
Guo, D., Dunbar, J. D., Yang, C. H., Pfeffer, L. M., & Donner, D. B. (1998). Induction of Jak/STAT Signaling by Activation of the Type 1 TNF Receptor. The Journal of Immunology, 160(6), 2742â2750.
Authors 5
DanQun Guo (first)
James D. Dunbar (additional)
Chuan He Yang (additional)
Lawrence M. Pfeffer (additional)
David B. Donner (additional)
References 71 Referenced 132
Dates
Type	When
Created	2 years, 8 months ago (Dec. 31, 2022, 9:17 a.m.)
Deposited	8 months ago (Jan. 2, 2025, 12:50 p.m.)
Indexed	31 minutes ago (Sept. 6, 2025, 12:14 p.m.)
Issued	27 years, 5 months ago (March 15, 1998)
Published	27 years, 5 months ago (March 15, 1998)
Published Print	27 years, 5 months ago (March 15, 1998)
Funders 0
None
BibTeX
@article{Guo_1998, title={Induction of Jak/STAT Signaling by Activation of the Type 1 TNF Receptor}, volume={160}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.160.6.2742}, DOI={10.4049/jimmunol.160.6.2742}, number={6}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Guo, DanQun and Dunbar, James D. and Yang, Chuan He and Pfeffer, Lawrence M. and Donner, David B.}, year={1998}, month=mar, pages={2742–2750} }
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  "abstract": "<jats:title>Abstract</jats:title><jats:p>Cellular responses to TNF are initiated by either of two cell surface receptors, the type 1 TNF receptor (TNFR1) and the type 2 TNF receptor (TNFR2). Although neither receptor contains an intrinsic protein tyrosine kinase, such activity has been implicated in TNF action. In this study, we show that murine TNF induces the tyrosine phosphorylation and activation of the intracellular Janus tyrosine kinases Jak1, Jak2, and Tyk2 in murine 3T3-L1 adipocytes. Activation of Jak kinases by TNF was associated with tyrosine phosphorylation of STAT1, STAT3, STAT5, and STAT6, but not STAT2 or STAT4, showing that TNF acts on a specific subset of these latent cytoplasmic transcription factors in 3T3-L1 adipocytes. Agonist antiserum to TNFR1 induced Jak kinase and STAT protein phosphorylation. Phosphorylation of Jak proteins was also induced by human TNF, which selectively binds to TNFR1 on murine cells. 35S-labeled Jak kinases were precipitated from a cell-free system and from lysates of 3T3-L1 adipocytes by a glutathione S-transferase fusion protein containing the cytoplasmic domain of TNFR1. These results suggest that the cytoplasmic domain of TNFR1 can directly interact with and form signaling complexes with Jak kinases. Jak2 was precipitated from HeLa cells by antiserum to TNFR1, directly demonstrating their association in vivo. Thus, TNF activates a Jak/STAT signal-transduction cascade by acting through TNFR1.</jats:p>",
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