Overview:

ASK1, also known as MAPKKK5, is responsible for activating MKK3, MKK4 (SEK1), and MKK6. ASK1 is activated in cells treated with tumor necrosis factor-alpha and overexpression of ASK1 leads to increased apoptosis (1). ASK1 interacts with members of the TRAF family and is activated by TRAF2 in the TNF-signaling pathway leading to the activation of MKK4 and subsequently JNK. Thus, ASK1 is a mediator of TRAF2-induced JNK activation (2).

References:

1. Ichijo, H. et al: Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 275: 90-94, 1997.

2. Nishitoh, H. et al: ASK1 is essential for JNK/SAPK activation by TRAF2. Molec. Cell 2: 389-395, 1998.