Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways

H Ichijo, E Nishida, K Irie, P Dijke, M Saitoh… - Science, 1997 - science.org
H Ichijo, E Nishida, K Irie, P Dijke, M Saitoh, T Moriguchi, M Takagi, K Matsumoto…
Science, 1997science.org
Mitogen-activated protein (MAP) kinase cascades are activated in response to various
extracellular stimuli, including growth factors and environmental stresses. A MAP kinase
kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups
of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in
turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-
terminal kinase) and p38 subgroups of MAP kinases, respectively. Overexpression of ASK1 …
Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli, including growth factors and environmental stresses. A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. Overexpression of ASK1 induced apoptotic cell death, and ASK1 was activated in cells treated with tumor necrosis factor-α (TNF-α). Moreover, TNF-α-induced apoptosis was inhibited by a catalytically inactive form of ASK1. ASK1 may be a key element in the mechanism of stress- and cytokine-induced apoptosis.
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