Details

Autor(en) / Beteiligte

• Ng, Patrick W.P.
• Jänicke, Reiner U.
• Porter, Alan G.

Titel

Mutations Which Abolish Phosphorylation of the TRAF-Binding Domain of TNF Receptor 2 Enhance Receptor-Mediated NF-κB Activation

Ist Teil von

• Biochemical and biophysical research communications, 1998-03, Vol.244 (3), p.756-762

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1998

Link zum Volltext

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• We demonstrate that a 41 amino acid region (amino acids 379 to 419) in the cytoplasmic domain of tumor necrosis factor receptor 2 (TNFR2) is phosphorylated by unidentified kinase(s) bothin vitroandin vivo.This domain (denoted x1c) corresponds almost exactly to the previously identified TRAF-binding domain and is by itself sufficient as a substrate for phosphorylation. In addition, the x1c domain is also crucial for TNFR2-mediated NF-κB activation. The cytoplasmic domain of TNFR2 lacks tyrosines, and conversion of all 12 potential serine and threonine phosphorylation targets in x1c to alanines either had no effect on NF-κB activation or resulted in enhanced NF-κB activity, depending on the structural context of x1c. The results show that while the TRAF-binding domain of TNFR2 is a major target of kinases, its phosphorylation is not required for NF-κB activation. Our data moreover suggest that phosphorylation of x1c negatively regulates the activation of NF-κB.