| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*
Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202; and
Department of Pathology, University of Tennessee College of Medicine, Memphis, TN 38163
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.
This article has been cited by other articles:
|
|
 |
|
  R. Pincheira, A. F. Castro, O. N. Ozes, P. S. Idumalla, and D. B. Donner Type 1 TNF Receptor Forms a Complex with and Uses Jak2 and c-Src to Selectively Engage Signaling Pathways That Regulate Transcription Factor Activity J. Immunol., July 15, 2008; 181(2): 1288 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Warfel and F. D'Agnillo Anthrax Lethal Toxin Enhances TNF-Induced Endothelial VCAM-1 Expression via an IFN Regulatory Factor-1-Dependent Mechanism J. Immunol., June 1, 2008; 180(11): 7516 - 7524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Elsasser, T. J. Caperna, C-J. Li, S. Kahl, and J. L. Sartin Critical control points in the impact of the proinflammatory immune response on growth and metabolism J Anim Sci, April 1, 2008; 86(14_suppl): E105 - E125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kimura, S. Teranishi, K. Fukuda, K. Kawamoto, and T. Nishida Delayed Disruption of Barrier Function in Cultured Human Corneal Epithelial Cells Induced by Tumor Necrosis Factor-{alpha} in a Manner Dependent on NF-{kappa}B Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 565 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Tliba and Y. Amrani Airway Smooth Muscle Cell as an Inflammatory Cell: Lessons Learned from Interferon Signaling Pathways Proceedings of the ATS, January 1, 2008; 5(1): 106 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Elsasser, S. Kahl, C.-J. Li, J. L. Sartin, W. M. Garrett, and J. Rodrigo Caveolae Nitration of Janus Kinase-2 at the 1007Y-1008Y Site: Coordinating Inflammatory Response and Metabolic Hormone Readjustment within the Somatotropic Axis Endocrinology, August 1, 2007; 148(8): 3803 - 3813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Numata, M. Kubo, H. Watanabe, K. Takagi, H. Mizuta, S. Okada, S. L. Kunkel, T. Ito, and A. Matsukawa Overexpression of Suppressor of Cytokine Signaling-3 in T Cells Exacerbates Acetaminophen-Induced Hepatotoxicity J. Immunol., March 15, 2007; 178(6): 3777 - 3785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. E. Floyd, B. M. Segura, F. He, and J. M. Stephens Degradation of STAT5 proteins in 3T3-L1 adipocytes is induced by TNF-{alpha} and cycloheximide in a manner independent of STAT5A activation Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E461 - E468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Theiss, J. G. Simmons, C. Jobin, and P. K. Lund Tumor Necrosis Factor (TNF) {alpha} Increases Collagen Accumulation and Proliferation in Intestinal Myofibroblasts via TNF Receptor 2 J. Biol. Chem., October 28, 2005; 280(43): 36099 - 36109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Peppel, L. Zhang, E. S. Orman, P.-O. Hagen, A. Amalfitano, L. Brian, and N. J. Freedman Activation of vascular smooth muscle cells by TNF and PDGF: overlapping and complementary signal transduction mechanisms Cardiovasc Res, February 15, 2005; 65(3): 674 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kimura, T. Naka, S. Nagata, I. Kawase, and T. Kishimoto SOCS-1 suppresses TNF-{alpha}-induced apoptosis through the regulation of Jak activation Int. Immunol., July 1, 2004; 16(7): 991 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sriram, S. A. Benkovic, M. A. Hebert, D. B. Miller, and J. P. O'Callaghan Induction of gp130-related Cytokines and Activation of JAK2/STAT3 Pathway in Astrocytes Precedes Up-regulation of Glial Fibrillary Acidic Protein in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Model of Neurodegeneration: KEY SIGNALING PATHWAY FOR ASTROGLIOSIS IN VIVO? J. Biol. Chem., May 7, 2004; 279(19): 19936 - 19947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Bharti, S. Shishodia, J. M. Reuben, D. Weber, R. Alexanian, S. Raj-Vadhan, Z. Estrov, M. Talpaz, and B. B. Aggarwal Nuclear factor-{kappa}B and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis Blood, April 15, 2004; 103(8): 3175 - 3184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Tliba, S. Tliba, C. Da Huang, R. K. Hoffman, P. DeLong, R. A. Panettieri Jr., and Y. Amrani Tumor Necrosis Factor {alpha} Modulates Airway Smooth Muscle Function via the Autocrine Action of Interferon {beta} J. Biol. Chem., December 12, 2003; 278(50): 50615 - 50623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Wesemann and E. N. Benveniste STAT-1{alpha} and IFN-{gamma} as Modulators of TNF-{alpha} Signaling in Macrophages: Regulation and Functional Implications of the TNF Receptor 1:STAT-1{alpha} Complex J. Immunol., November 15, 2003; 171(10): 5313 - 5319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Bharti, N. Donato, and B. B. Aggarwal Curcumin (Diferuloylmethane) Inhibits Constitutive and IL-6-Inducible STAT3 Phosphorylation in Human Multiple Myeloma Cells J. Immunol., October 1, 2003; 171(7): 3863 - 3871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Wesemann, Y. Dong, G. M. O'Keefe, V. T. Nguyen, and E. N. Benveniste Suppressor of Cytokine Signaling 1 Inhibits Cytokine Induction of CD40 Expression in Macrophages J. Immunol., September 1, 2002; 169(5): 2354 - 2360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cottet, P. Dupraz, F. Hamburger, W. Dolci, M. Jaquet, and B. Thorens cFLIP Protein Prevents Tumor Necrosis Factor-{alpha}-Mediated Induction of Caspase-8-Dependent Apoptosis in Insulin-Secreting {beta}Tc-Tet Cells Diabetes, June 1, 2002; 51(6): 1805 - 1814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Machinal-Quelin, M. N. Dieudonne, M. C. Leneveu, R. Pecquery, and Y. Giudicelli Proadipogenic effect of leptin on rat preadipocytes in vitro: activation of MAPK and STAT3 signaling pathways Am J Physiol Cell Physiol, April 1, 2002; 282(4): C853 - C863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-c. Kang, R. V. Gopalkrishnan, Q. Wu, E. Jankowsky, A. M. Pyle, and P. B. Fisher mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties PNAS, January 22, 2002; 99(2): 637 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Miscia, M. Marchisio, A. Grilli, V. Di Valerio, L. Centurione, G. Sabatino, F. Garaci, G. Zauli, E. Bonvini, and A. Di Baldassarre Tumor Necrosis Factor {alpha} (TNF-{alpha}) Activates Jak1/Stat3-Stat5B Signaling through TNFR-1 in Human B Cells Cell Growth Differ., January 1, 2002; 13(1): 13 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Emanuelli, P. Peraldi, C. Filloux, C. Chavey, K. Freidinger, D. J. Hilton, G. S. Hotamisligil, and E. Van Obberghen SOCS-3 Inhibits Insulin Signaling and Is Up-regulated in Response to Tumor Necrosis Factor-alpha in the Adipose Tissue of Obese Mice J. Biol. Chem., December 14, 2001; 276(51): 47944 - 47949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zamorano, A. L. Mora, M. Boothby, and A. D. Keegan NF-{kappa}B activation plays an important role in the IL-4-induced protection from apoptosis Int. Immunol., December 1, 2001; 13(12): 1479 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Rizk, D. Stammsen, G. Preibisch, and J. Eckel Leptin and Tumor Necrosis Factor-{{alpha}} Induce the Tyrosine Phosphorylation of Signal Transducer and Activator of Transcription Proteins in the Hypothalamus of Normal Rats In Vivo Endocrinology, July 1, 2001; 142(7): 3027 - 3032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hoeck and M. Woisetschlager STAT6 Mediates Eotaxin-1 Expression in IL-4 or TNF-{{alpha}}-Induced Fibroblasts J. Immunol., April 1, 2001; 166(7): 4507 - 4515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Hiraoka, S. Kawashima, T. Takahashi, Y. Rikitake, T. Kitamura, W. Ogawa, and M. Yokoyama TNF-{alpha} induces protein synthesis through PI3-kinase-Akt/PKB pathway in cardiac myocytes Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1861 - H1868. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bhattacharya, B. A. Stout, M. E. Bates, P. J. Bertics, and J. S. Malter Granulocyte Macrophage Colony-Stimulating Factor and Interleukin-5 Activate STAT5 and Induce CIS1 mRNA in Human Peripheral Blood Eosinophils Am. J. Respir. Cell Mol. Biol., March 1, 2001; 24(3): 312 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Allendoerfer and G. S. Deepe Jr. Regulation of Infection with Histoplasma capsulatum by TNFR1 and -2 J. Immunol., September 1, 2000; 165(5): 2657 - 2664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, T. R. Wu, S. Cai, T. Welte, and Y. E. Chin Stat1 as a Component of Tumor Necrosis Factor Alpha Receptor 1-TRADD Signaling Complex To Inhibit NF-kappa B Activation Mol. Cell. Biol., July 1, 2000; 20(13): 4505 - 4512. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Baetta, M. Soma, C. De-Fraja, C. Comparato, C. Teruzzi, L. Magrassi, and E. Cattaneo Upregulation and Activation of Stat6 Precede Vascular Smooth Muscle Cell Proliferation in Carotid Artery Injury Model Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 931 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Matsukura, C. Stellato, J. R. Plitt, C. Bickel, K. Miura, S. N. Georas, V. Casolaro, and R. P. Schleimer Activation of Eotaxin Gene Transcription by NF-{kappa}B and STAT6 in Human Airway Epithelial Cells J. Immunol., December 15, 1999; 163(12): 6876 - 6883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sato, H. Nagayama, K. Tadokoro, T. Juji, and T. A. Takahashi Extracellular Signal-Regulated Kinase, Stress-Activated Protein Kinase/c-Jun N-Terminal Kinase, and p38mapk Are Involved in IL-10-Mediated Selective Repression of TNF-{alpha}-Induced Activation and Maturation of Human Peripheral Blood Monocyte-Derived Dendritic Cells J. Immunol., April 1, 1999; 162(7): 3865 - 3872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Constantin, C. Laudanna, S. Brocke, and E. C. Butcher Inhibition of Experimental Autoimmune Encephalomyelitis by a Tyrosine Kinase Inhibitor J. Immunol., January 15, 1999; 162(2): 1144 - 1149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Towne, C. M. Krane, C. J. Bachurski, and A. G. Menon Tumor Necrosis Factor-alpha Inhibits Aquaporin 5 Expression in Mouse Lung Epithelial Cells J. Biol. Chem., May 25, 2001; 276(22): 18657 - 18664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Craig, A. Larkin, A. M. Mingo, D. J. Thuerauf, C. Andrews, P. M. McDonough, and C. C. Glembotski p38 MAPK and NF-kappa B Collaborate to Induce Interleukin-6 Gene Expression and Release. EVIDENCE FOR A CYTOPROTECTIVE AUTOCRINE SIGNALING PATHWAY IN A CARDIAC MYOCYTE MODEL SYSTEM J. Biol. Chem., July 28, 2000; 275(31): 23814 - 23824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Morita, T. Naka, Y. Kawazoe, M. Fujimoto, M. Narazaki, R. Nakagawa, H. Fukuyama, S. Nagata, and T. Kishimoto Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis factor alpha -induced cell death in fibroblasts PNAS, May 9, 2000; 97(10): 5405 - 5410. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
