scholarly journals Tumor necrosis factor receptor-associated factor-6 and ribosomal S6 kinase intracellular pathways link the angiotensin II AT1 receptor to the phosphorylation and activation of the IκB kinase complex in vascular smooth muscle cells.

2011 ◽  
Vol 286 (12) ◽  
pp. 10888.1-10888
Author(s):  
Priscilla Doyon ◽  
Marc J. Servant
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
S6 Kinase ◽  
Iκb Kinase ◽  
Intracellular Pathways ◽  
Ribosomal S6 Kinase ◽  
Necrosis Factor

Tumor Necrosis Factor Receptor-Associated Factor 5 Promotes Arterial Neointima Formation through Smooth Muscle Cell Proliferation

2019 ◽  
Vol 56 (6) ◽  
pp. 308-319
Author(s):  
Florian Willecke ◽  
Benjamin Rupprecht ◽  
Mark Colin Gissler ◽  
Katharina Pfeiffer ◽  
Nathaly Anto-Michel ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Tumor Necrosis Factor ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Smooth Muscle Cell Proliferation ◽  
Neointima Formation ◽  
Necrosis Factor

scholarly journals Regulation of tumor necrosis factor receptor-1 and the IKK-NF-κB pathway by LDL receptor–related protein explains the antiinflammatory activity of this receptor

Blood ◽  
2008 ◽  
Vol 111 (11) ◽  
pp. 5316-5325 ◽  
Author(s):  
Alban Gaultier ◽  
Sanja Arandjelovic ◽  
Sherry Niessen ◽  
Cheryl D. Overton ◽  
MacRae F. Linton ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Cell Surface ◽  
Cell Signaling ◽  
Inflammatory Mediators ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Protein Profiling ◽  
Related Protein ◽  
Iκb Kinase ◽  
Necrosis Factor

Abstract Low-density lipoprotein receptor–related protein (LRP-1) functions in endocytosis and in cell signaling directly (by binding signaling adaptor proteins) or indirectly (by regulating levels of other cell-surface receptors). Because recent studies in rodents suggest that LRP-1 inhibits inflammation, we conducted activity-based protein profiling experiments to discover novel proteases, involved in inflammation, that are regulated by LRP-1. We found that activated complement proteases accumulate at increased levels when LRP-1 is absent. Although LRP-1 functions as an endocytic receptor for C1r and C1s, complement protease mRNA expression was increased in LRP-1–deficient cells, as was expression of inducible nitric oxide synthase (iNOS) and interleukin-6. Regulation of expression of inflammatory mediators was explained by the ability of LRP-1 to suppress basal cell signaling through the IκB kinase–nuclear factor-κB (NF-κB) pathway. LRP-1–deficient macrophages, isolated from mice, demonstrated increased expression of iNOS, C1r, and monocyte chemoattractant protein-1 (MCP-1); MCP-1 expression was inhibited by NF-κB antagonism. The mechanism by which LRP-1 inhibits NF-κB activity involves down-regulating cell-surface tumor necrosis factor receptor-1 (TNFR1) and thus, inhibition of autocrine TNFR1-initiated cell signaling. TNF-α–neutralizing antibody inhibited NF-κB activity selectively in LRP-1–deficient cells. We propose that LRP-1 suppresses expression of inflammatory mediators indirectly, by regulating TNFR1-dependent cell signaling through the IκB kinase–NF-κB pathway.

scholarly journals TRAF6 and the Three C-Terminal Lysine Sites on IRF7 Are Required for Its Ubiquitination-Mediated Activation by the Tumor Necrosis Factor Receptor Family Member Latent Membrane Protein 1

2008 ◽  
Vol 28 (20) ◽  
pp. 6536-6546 ◽  
Author(s):  
Shunbin Ning ◽  
Alex D. Campos ◽  
Bryant G. Darnay ◽  
Gretchen L. Bentz ◽  
Joseph S. Pagano
Keyword(s):  
Tumor Necrosis Factor ◽  
Membrane Protein ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
E3 Ligase ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 1 ◽  
Iκb Kinase ◽  
Necrosis Factor

ABSTRACT We have recently shown that interferon regulatory factor 7 (IRF7) is activated by Epstein-Barr virus latent membrane protein 1 (LMP1), a member of the tumor necrosis factor receptor (TNFR) superfamily, through receptor-interacting protein-dependent K63-linked ubiquitination (L. E. Huye, S. Ning, M. Kelliher, and J. S. Pagano, Mol. Cell. Biol. 27:2910-2918, 2007). In this study, with the use of small interfering RNA and TNFR-associated factor 6 (TRAF6) knockout cells, we first show that TRAF6 and its E3 ligase activity are required for LMP1-stimulated IRF7 ubiquitination. In Raji cells which are latently infected and express high levels of LMP1 and IRF7 endogenously, expression of a TRAF6 small hairpin RNA construct reduces endogenous ubiquitination and endogenous activity of IRF7. In TRAF6−/− mouse embryonic fibroblasts, reconstitution with TRAF6 expression, but not with TRAF6(C70A), which lacks the E3 ligase activity, recovers LMP1's ability to stimulate K63-linked ubiquitination of IRF7. Further, we identify IRF7 as a substrate for TRAF6 E3 ligase and show that IRF7 is ubiquitinated by TRAF6 at multiple sites both in vitro and in vivo. Most important, we determine that the last three C-terminal lysine sites (positions 444, 446, and 452) of human IRF7 variant A are essential for activation of IRF7; these are the first such sites identified. A ubiquitination-deficient mutant of IRF7 with these sites mutated to arginines completely loses transactivational ability in response not only to LMP1 but also to the IRF7 kinase IκB kinase ε. In addition, we find that K63-linked ubiquitination of IRF7 occurs independently of its C-terminal functional phosphorylation sites. These data support our hypothesis that regulatory ubiquitination of IRF7 is a prerequisite for its phosphorylation. This is the first evidence to imply that ubiquitination is required for phosphorylation and activation of a transcription factor.

scholarly journals Control Sites of Ribosomal S6 Kinase B and Persistent Activation through Tumor Necrosis Factor

2000 ◽  
Vol 275 (31) ◽  
pp. 23549-23558 ◽  
Author(s):  
Mar Tomás-Zuber ◽  
Jean-Luc Mary ◽  
Werner Lesslauer
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
S6 Kinase ◽  
Ribosomal S6 Kinase ◽  
Necrosis Factor
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