ASK1 Antibody – Rabbit Polyclonal

Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]

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: EC 2.7.11.25; 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

Molecular Function: ATP binding; magnesium ion binding; MAP kinase kinase kinase activity; protein 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; 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; protein amino acid phosphorylation