- ASK-1
Apoptosis signal-regulating kinase 1, ASK-1, is part of the
mitogen-activated protein kinase (MAPK) cascade. In humans it is also known as "mitogen-activated protein kinase kinase kinase 5", abbreviated as "MAP3K5".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.Phosphorylation of ASK-1 protein can lead toapoptosis or other cellular responses depending on the cell type.Northern blot analysis shows that ASK-1 transcript is abundantly expressed in human heart and pancreas. The ASK-1 (MAPKKK5) protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activatesc-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; ASK-1 does not activate MAPK/ERK. [cite web | title = Entrez Gene: MAP3K5 mitogen-activated protein kinase kinase kinase 5| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4217| accessdate = ]ASK-1 found in the inactive form, bound to reduced
thioredoxin . When oxidized by areactive oxygen species , Trx dissociates from ASK-1. The ASK-1, which is found as a homo-oligodimer, autophosphorylates and becomes an active MAP kinase kinase kinase.ASK-1 contains 1,374 amino acids with all 11 kinase subdomains. It is located on chromosome 6 at locus 6q22.33.
References
Further reading
*cite journal |author=Hayakawa T, Matsuzawa A, Noguchi T, Takeda K, Ichijo H |title=The ASK1-MAP kinase pathways in immune and stress responses |journal=Microbes Infect. |volume=8 |issue=4 |pages=1098–107 |year=2006 |pmid=16517200 |doi=10.1016/j.micinf.2005.12.001PBB_Further_reading
citations =
*cite journal | author=Nagai H, Noguchi T, Takeda K, Ichijo H |title=Pathophysiological roles of ASK1-MAP kinase signaling pathways. |journal=J. Biochem. Mol. Biol. |volume=40 |issue= 1 |pages= 1–6 |year= 2007 |pmid= 17244475 |doi=
*cite journal | author=Wang XS, Diener K, Jannuzzi D, "et al." |title=Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase. |journal=J. Biol. Chem. |volume=271 |issue= 49 |pages= 31607–11 |year= 1997 |pmid= 8940179 |doi=
*cite journal | author=Ichijo H, Nishida E, Irie K, "et al." |title=Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. |journal=Science |volume=275 |issue= 5296 |pages= 90–4 |year= 1997 |pmid= 8974401 |doi=
*cite journal | author=Rampoldi L, Zimbello R, Bortoluzzi S, "et al." |title=Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5. |journal=Cytogenet. Cell Genet. |volume=78 |issue= 3-4 |pages= 301–3 |year= 1998 |pmid= 9465908 |doi=
*cite journal | author=Saitoh M, Nishitoh H, Fujii M, "et al." |title=Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. |journal=EMBO J. |volume=17 |issue= 9 |pages= 2596–606 |year= 1998 |pmid= 9564042 |doi= 10.1093/emboj/17.9.2596
*cite journal | author=Gotoh Y, Cooper JA |title=Reactive oxygen species- and dimerization-induced activation of apoptosis signal-regulating kinase 1 in tumor necrosis factor-alpha signal transduction. |journal=J. Biol. Chem. |volume=273 |issue= 28 |pages= 17477–82 |year= 1998 |pmid= 9651337 |doi=
*cite journal | author=Chang HY, Nishitoh H, Yang X, "et al." |title=Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx. |journal=Science |volume=281 |issue= 5384 |pages= 1860–3 |year= 1998 |pmid= 9743501 |doi=
*cite journal | author=Nishitoh H, Saitoh M, Mochida Y, "et al." |title=ASK1 is essential for JNK/SAPK activation by TRAF2. |journal=Mol. Cell |volume=2 |issue= 3 |pages= 389–95 |year= 1998 |pmid= 9774977 |doi=
*cite journal | author=Wang XS, Diener K, Tan TH, Yao Z |title=MAPKKK6, a novel mitogen-activated protein kinase kinase kinase, that associates with MAPKKK5. |journal=Biochem. Biophys. Res. Commun. |volume=253 |issue= 1 |pages= 33–7 |year= 1999 |pmid= 9875215 |doi= 10.1006/bbrc.1998.9749
*cite journal | author=Zhang L, Chen J, Fu H |title=Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 15 |pages= 8511–5 |year= 1999 |pmid= 10411906 |doi=
*cite journal | author=Hoeflich KP, Yeh WC, Yao Z, "et al." |title=Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1). |journal=Oncogene |volume=18 |issue= 42 |pages= 5814–20 |year= 1999 |pmid= 10523862 |doi= 10.1038/sj.onc.1202975
*cite journal | author=Takeda K, Hatai T, Hamazaki TS, "et al." |title=Apoptosis signal-regulating kinase 1 (ASK1) induces neuronal differentiation and survival of PC12 cells. |journal=J. Biol. Chem. |volume=275 |issue= 13 |pages= 9805–13 |year= 2000 |pmid= 10734135 |doi=
*cite journal | author=Mochida Y, Takeda K, Saitoh M, "et al." |title=ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction. |journal=J. Biol. Chem. |volume=275 |issue= 42 |pages= 32747–52 |year= 2000 |pmid= 10921914 |doi= 10.1074/jbc.M003042200
*cite journal | author=Charette SJ, Lavoie JN, Lambert H, Landry J |title=Inhibition of Daxx-mediated apoptosis by heat shock protein 27. |journal=Mol. Cell. Biol. |volume=20 |issue= 20 |pages= 7602–12 |year= 2000 |pmid= 11003656 |doi=
*cite journal | author=McDonald PH, Chow CW, Miller WE, "et al." |title=Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. |journal=Science |volume=290 |issue= 5496 |pages= 1574–7 |year= 2000 |pmid= 11090355 |doi=
*cite journal | author=Ko YG, Kim EY, Kim T, "et al." |title=Glutamine-dependent antiapoptotic interaction of human glutaminyl-tRNA synthetase with apoptosis signal-regulating kinase 1. |journal=J. Biol. Chem. |volume=276 |issue= 8 |pages= 6030–6 |year= 2001 |pmid= 11096076 |doi= 10.1074/jbc.M006189200
*cite journal | author=Kim AH, Khursigara G, Sun X, "et al." |title=Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. |journal=Mol. Cell. Biol. |volume=21 |issue= 3 |pages= 893–901 |year= 2001 |pmid= 11154276 |doi= 10.1128/MCB.21.3.893-901.2001
*cite journal | author=Cho SG, Lee YH, Park HS, "et al." |title=Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1. |journal=J. Biol. Chem. |volume=276 |issue= 16 |pages= 12749–55 |year= 2001 |pmid= 11278289 |doi= 10.1074/jbc.M005561200
*cite journal | author=Geleziunas R, Xu W, Takeda K, "et al." |title=HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell. |journal=Nature |volume=410 |issue= 6830 |pages= 834–8 |year= 2001 |pmid= 11298454 |doi= 10.1038/35071111
*cite journal | author=Xu XN, Screaton G |title=HIV-1 Nef: negative effector of Fas? |journal=Nat. Immunol. |volume=2 |issue= 5 |pages= 384–5 |year= 2001 |pmid= 11323689 |doi= 10.1038/87682PBB_Controls
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