ASK1 is essential for JNK/SAPK activation by TRAF2

Mol Cell. 1998 Sep;2(3):389-95. doi: 10.1016/s1097-2765(00)80283-x.

Abstract

Tumor necrosis factor (TNF)-induced activation of the c-jun N-terminal kinase (JNK, also known as SAPK; stress-activated protein kinase) requires TNF receptor-associated factor 2 (TRAF2). The apoptosis signal-regulating kinase 1 (ASK1) is activated by TNF and stimulates JNK activation. Here we show that ASK1 interacts with members of the TRAF family and is activated by TRAF2, TRAF5, and TRAF6 overexpression. A truncated derivative of TRAF2, which inhibits JNK activation by TNF, blocks TNF-induced ASK1 activation. A catalytically inactive mutant of ASK1 is a dominant-negative inhibitor of TNF- and TRAF2-induced JNK activation. In untransfected mammalian cells, ASK1 rapidly associates with TRAF2 in a TNF-dependent manner. Thus, ASK1 is a mediator of TRAF2-induced JNK activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Enzyme Activation
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • Mammals
  • Mitogen-Activated Protein Kinases*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*
  • Receptors, Tumor Necrosis Factor / metabolism
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 5
  • TNF Receptor-Associated Factor 6
  • Transfection

Substances

  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • TNF Receptor-Associated Factor 2
  • TNF Receptor-Associated Factor 5
  • TNF Receptor-Associated Factor 6
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases