Regulation of ASK1 signaling by scaffold and adaptor proteins

The mitogen-activated protein kinase (MAPK) signaling pathway is a three-tiered kinase cascade where mitogen-activated protein kinase kinase kinases (MAP3Ks) lead to the activation of mitogen-activated protein kinase kinases (MAP2K), and ultimately MAPK proteins. MAPK signaling can promote a diverse set of biological outcomes, ranging from cell death to proliferation. There are multiple mechanisms which govern MAPK output, such as the duration and strength of the signal, cellular localization to upstream and downstream binding partners, pathway crosstalk and the binding to scaffold and adaptor molecules. This review will focus on scaffold and adaptor proteins that bind to and regulate apoptosis signal-regulating kinase 1 (ASK1), a MAP3K protein with a critical role in mediating stress response pathways.