CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase

J Biol Chem. 1998 May 22;273(21):13353-8. doi: 10.1074/jbc.273.21.13353.

Abstract

CD27 is a member of the tumor necrosis factor (TNF) receptor superfamily and is expressed on T, B, and NK cells. The signal via CD27 plays pivotal roles in T-T and T-B cell interactions. Here we demonstrate that overexpression of CD27 activates NF-kappaB and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK). Deletion analysis of the cytoplasmic domain of CD27 revealed that the C-terminal PIQEDYR motif was indispensable for both NF-kappaB and SAPK/JNK activation and was also required for the interaction with TNF receptor-associated factor (TRAF) 2 and TRAF5, both of which have been implicated in NF-kappaB activation by members of the TNF-R superfamily. Co-transfection of a dominant negative TRAF2 or TRAF5 blocked NF-kappaB and SAPK/JNK activation induced by CD27. Recently, a TRAF2-interacting kinase has been identified, termed NF-kappaB-inducing kinase (NIK). A kinase-inactive mutant NIK blocked CD27-, TRAF2-, and TRAF5-mediated NF-kappaB and SAPK/JNK activation. These results indicate that TRAF2 and TRAF5 are involved in NF-kappaB and SAPK/JNK activation by CD27, and NIK is a common downstream kinase of TRAF2 and TRAF5 for NF-kappaB and SAPK/JNK activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Enzyme Activation
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases*
  • NF-kappa B / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proteins / metabolism*
  • Receptors, Tumor Necrosis Factor / metabolism
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 5
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism*

Substances

  • NF-kappa B
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 5
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • NF-kappa B kinase