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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. Note: This description may include information from UniProtKB.
Protein type: EC; Kinase, protein; Protein kinase, STE; Protein kinase, Ser/Thr (non-receptor); STE group; STE11 family
Chromosomal Location of Human Ortholog: 6q23.3
Cellular Component: cytosol; protein complex
Molecular Function: ATP binding; magnesium ion binding; MAP kinase kinase kinase activity; protein binding; protein domain specific binding; protein homodimerization activity; protein kinase activity; protein phosphatase binding; protein serine/threonine kinase activity
Biological Process: activation of JNK activity; activation of MAPKK activity; cellular response to amino acid starvation; induction of apoptosis by oxidative stress; 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 transcription, DNA-dependent; protein amino acid phosphorylation; stress-activated MAPK cascade
Reference #:  Q99683 (UniProtKB)
Alt. Names/Synonyms: apoptosis signal regulating kinase 1; apoptosis signal-regulating kinase 1; ASK-1; ASK1; MAP/ERK kinase kinase 5; MAP3K5; MAPK/ERK kinase kinase 5; MAPKKK5; MEK kinase 5; MEKK 5; MEKK5; mitogen-activated protein kinase kinase kinase 5; Mitogen-activated protein kinase kinase kinase 5 variant
Gene Symbols: MAP3K5
Molecular weight: 154,537 Da
Basal Isoelectric point: 5.52  Predict pI for various phosphorylation states
CST Pathways:  Actin Dynamics  |  Apoptosis Regulation  |  B Cell Receptor Signaling  |  Death Receptor Signaling  |  Regulation of P38 MAPKs  |  SAPK/JNK Signaling Cascades
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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