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. Note: This description may include information from UniProtKB.
Protein type: Kinase, protein; EC 22.214.171.124; Protein kinase, STE; Protein kinase, Ser/Thr (non-receptor); STE group; STE11 family
Molecular Function: ATP binding; magnesium ion binding; MAP kinase kinase kinase activity; protein binding; protein homodimerization activity; protein kinase activity; protein kinase binding; protein phosphatase binding; protein serine/threonine kinase activity
Biological Process: activation of JNK activity; activation of MAPKK activity; induction of apoptosis by oxidative stress; innate immune response; JNK cascade; MAPKKK cascade; positive regulation of apoptosis; positive regulation of caspase activity; positive regulation of JNK activity; positive regulation of JNK cascade; positive regulation of myoblast differentiation; protein amino acid phosphorylation; viral reproduction
LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.