Apoptosis signal-regulating kinase 1 (ASK1), a MAP kinase kinase kinase, plays essential roles in stress-induced apoptosis. ASK1 is activated in response to a variety of stress-related stimuli through distinct mechanisms and activates MKK4 and MKK3, which in turn activate JNK and p38. Overexpression of ASK1 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 and cell death. Phosphorylation at Ser967 is essential for ASK1 association with 14-3-3 protein and suppression of cell death. Oxidative stress induces dephosphorylation of Ser967 and phosphorylation of Thr845 in the activation loop of ASK1, and both are correlated with ASK1 activity and ASK1-dependent apoptosis. On the other hand, Akt phosphorylates ASK1 at Ser83, which attenuates ASK1 activity and promotes cell survival.
Apoptosis signal-regulating kinase 1 (ASK1), a MAP kinase kinase kinase, plays essential roles in stress-induced apoptosis. ASK1 is activated in response to a variety of stress-related stimuli through distinct mechanisms and activates MKK4 and MKK3, which in turn activate JNK and p38. Overexpression of ASK1 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 and cell death. Phosphorylation at Ser967 is essential for ASK1 association with 14-3-3 protein and suppression of cell death. Oxidative stress induces dephosphorylation of Ser967 and phosphorylation of Thr845 in the activation loop of ASK1, and both are correlated with ASK1 activity and ASK1-dependent apoptosis. On the other hand, Akt phosphorylates ASK1 at Ser83, which attenuates ASK1 activity and promotes cell survival.
Size
100μl(100μg)
Species
Homo Sapiens (Human)
Subcellular Location
Cytoplasm, Endoplasmic reticulum
Target Details
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.
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).
Pathway
MAPK signaling pathway TNF signaling pathway Apoptosis Protein processing in endoplasmic reticulum ER Stress pathway Neurotrophin signaling pathway
Protein Families
Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
Tissue Specificity
Abundantly expressed in heart and pancreas.
Weight
69,839 Da
Buffer
Buffer: PBS with 0.02% sodium azide, 50% glycerol, pH7.3.
Format
liquid
Purification
Affinity purification
Purity
Affinity purification
Storage
Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.
Storage Buffer
Store at -20oC or -80oC. Avoid freeze / thaw cycles. Buffer: PBS with 0.02% sodium azide, 50% glycerol, pH7.3.