Anti-ASK1

Ask1 (apoptosis signal-regulating kinase 1), a serine/threonine kinase, is a member of the MAPKKK family that constitutes the JNK and p38 (MAPK) cascades. Members of this family are activated by physiological and cytotoxic stresses and induce various stress responses including apoptosis. Specifically, Ask1-MAPK cascades have been shown to be involved in endoplasmic reticululum (ER) stress-induced apoptosis and in neuronal cell death. Studies suggest that ER stress-induced apoptosis plays critical roles in the pathogenesis in some neurodegenerative diseases including Alzheimer's, Parkinson's, polyglutamine (polyQ), amyotrophic lateral sclerosis (ALS) and Prion diseases. However, the regulation and function of Ask1 in neuronal cell death remains to be fully elucidated. In addition to playing a role in ER stress-induced apoptosis, Ask1 is also thought to be important in cytokine-induced apoptosis, and may also have functions other than apoptosis including roles in cell survival and differentiation. Structurally, human Ask1 has a serine/threonine kinase domain in the middle of the molecule. The kinase domain is evolutionarily conserved from nematode to human. A threonine residue with the activation loop of the kinases domain (Thr838 of human Ask1) is essential for Ask1 activation. There are two coiled-coil domains, one in the N-terminal and the other in the C-terminal domain. The coiled-coil domain in the C-terminal domain has been shown to be required for homo-oligomerzation. Protein function: 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). [The UniProt Consortium]