[PDF][PDF] ASK1 is essential for JNK/SAPK activation by TRAF2
H Nishitoh, M Saitoh, Y Mochida, K Takeda, H Nakano… - Molecular cell, 1998 - cell.com
H Nishitoh, M Saitoh, Y Mochida, K Takeda, H Nakano, M Rothe, K Miyazono, H Ichijo
Molecular cell, 1998•cell.comTumor 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 …
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 …
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.
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