ASK1: a MAP kinase kinase kinase of the STE11 family, apoptosis signal-regulating kinase 1 (ASK1) plays essential roles in stress-induced apoptosis. Activated by various stressors, including oxidative stress, endoplasmic reticulum stress, and calcium overload, as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) and lipopolysaccharide (LPS). In turn, ASK1 phosphorylates and activates two different subgroups of MAP kinase kinases, MKK4/SEK1 and MKK3/MKK6, which in turn activate stress-activated protein kinases (JNKs) and p38 subgroups of MAP kinases, respectively. Overexpression activates JNK and p38 and induces apoptosis in several cell types through signals involving the mitochondrial cell death pathway. Embryonic fibroblasts or primary neurons derived from ASK1-/- mice are resistant to stress-induced JNK and p38 activation as well as cell death. Oxidative stress induces the activation of ASK1, which correlate with ASK1 activity and ASK1-dependent apoptosis. Required for the innate immune response, which is essential for host defense against a wide range of pathogens.
Protein type: Protein kinase, STE; Protein kinase, Ser/Thr (non-receptor); Kinase, protein; EC 2.7.11.25; STE group; STE11 family
Cellular Component: endoplasmic reticulum; cytoplasm; intracellular
Molecular Function: protein homodimerization activity; metal ion binding; nucleotide binding; magnesium ion binding; caspase activator activity; protein phosphatase binding; protein kinase binding; protein kinase activity; transferase activity; protein serine/threonine kinase activity; protein binding; MAP kinase kinase kinase activity; transferase activity, transferring phosphorus-containing groups; kinase activity; ATP binding
Biological Process: caspase activation; positive regulation of JNK activity; activation of MAPKK activity; positive regulation of apoptosis; immune system process; activation of MAPK activity; apoptosis; MAPKKK cascade; positive regulation of caspase activity; protein amino acid phosphorylation; innate immune response; JNK cascade; positive regulation of protein amino acid phosphorylation; phosphorylation; induction of apoptosis by oxidative stress
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