scholarly journals Tumor Necrosis Factor (TNF)-induced Germinal Center Kinase-related (GCKR) and Stress-activated Protein Kinase (SAPK) Activation Depends upon the E2/E3 Complex Ubc13-Uev1A/TNF Receptor-associated Factor 2 (TRAF2)

2003 ◽  
Vol 278 (17) ◽  
pp. 15429-15434 ◽  
Author(s):  
Chong-Shan Shi ◽  
John H. Kehrl
Keyword(s):  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Germinal Center ◽  
Tumor Necrosis ◽  
Tnf Receptor ◽  
Associated Factor ◽  
Necrosis Factor

scholarly journals TANK Potentiates Tumor Necrosis Factor Receptor-Associated Factor-Mediated c-Jun N-Terminal Kinase/Stress-Activated Protein Kinase Activation through the Germinal Center Kinase Pathway

1999 ◽  
Vol 19 (10) ◽  
pp. 6665-6672 ◽  
Author(s):  
Arnold I-Dah Chin ◽  
Junyan Shu ◽  
Chong Shan Shi ◽  
Zhengbin Yao ◽  
John H. Kehrl ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Germinal Center ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Nuclear Factor Κb ◽  
Intramolecular Interactions ◽  
Tnf Receptor ◽  
Cell Functions ◽  
Necrosis Factor

ABSTRACT Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are mediators of many members of the TNF receptor superfamily and can activate both the nuclear factor κB (NF-κB) and stress-activated protein kinase (SAPK; also known as c-Jun N-terminal kinase) signal transduction pathways. We previously described the involvement of a TRAF-interacting molecule, TRAF-associated NF-κB activator (TANK), in TRAF2-mediated NF-κB activation. Here we show that TANK synergized with TRAF2, TRAF5, and TRAF6 but not with TRAF3 in SAPK activation. TRAF2 and TANK individually formed weak interactions with germinal center kinase (GCK)-related kinase (GCKR). However, when coexpressed, they formed a strong complex with GCKR, thereby providing a potential mechanism for TRAF and TANK synergy in GCKR-mediated SAPK activation, which is important in TNF family receptor signaling. Our results also suggest that TANK can form potential intermolecular as well as intramolecular interactions between its amino terminus and carboxyl terminus. This study suggests that TANK is a regulatory molecule controlling the threshold of NF-κB and SAPK activities in response to activation of TNF receptors. In addition, CD40 activated endogenous GCKR in primary B cells, implicating GCK family proteins in CD40-mediated B-cell functions.

scholarly journals Downregulation of tumor necrosis factor (TNF) sensitivity via modulation of TNF binding capacity by protein kinase C activators.

1987 ◽  
Vol 166 (6) ◽  
pp. 1788-1797 ◽  
Author(s):  
R Unglaub ◽  
B Maxeiner ◽  
B Thoma ◽  
K Pfizenmaier ◽  
P Scheurich
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Binding Capacity ◽  
Receptor Protein ◽  
Tnf Alpha ◽  
Tnf Receptor ◽  
Kinase C ◽  
Necrosis Factor

The regulatory action of activators for protein kinase C on the specific binding capacity for recombinant human tumor necrosis factor alpha (TNF-alpha) was studied on various human cell lines. Phorbol myristate acetate (PMA) and oleyl acetyl glycerol (OAG) both are able to rapidly downregulate TNF-binding capacity of normal and malignant cells derived from various tissues. As PMA treatment did not enhance internalization of TNF-alpha-receptor complexes at 37 degrees C, and since OAG was able to downregulate TNF-binding capacity under conditions where internalization and shedding of receptor protein are prevented, we conclude that protein kinase C controls ligand affinity of the TNF-receptor protein, possibly via direct phosphorylation. Protein kinase C triggered downregulation of TNF-alpha-binding capacity concomitantly resulted in reduction of TNF-alpha sensitivity, as revealed from decreased cytotoxic action of TNF-alpha on L 929 cells and from inhibition of TNF-alpha-mediated enhancement of HLA class II antigen expression in Colo 205 cells. Restoration of TNF-binding capacity upon abrogation of protein kinase C stimulation leads to full recovery of TNF responsiveness, further supporting the close linkage of TNF-receptor expression and TNF sensitivity. These data suggest that regulation of TNF-binding capacity by protein kinase C is one of the cellular control mechanisms of TNF responsiveness.

scholarly journals Intracellular localization and transcriptional regulation of tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4)

2002 ◽  
Vol 269 (19) ◽  
pp. 4819-4829 ◽  
Author(s):  
Heike Glauner ◽  
Daniela Siegmund ◽  
Hassan Motejadded ◽  
Peter Scheurich ◽  
Frank Henkler ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Intracellular Localization ◽  
Tnf Receptor ◽  
Associated Factor ◽  
Necrosis Factor
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