Map3k5

Summary

Gene Symbol: Map3k5
Description: mitogen-activated protein kinase kinase kinase 5
Alias: 7420452D20Rik, ASK, ASK1, MAPKKK5, Mekk5, mitogen-activated protein kinase kinase kinase 5, ASK-1, MAPK/ERK kinase kinase 5, MEK kinase 5, MEKK 5, apoptosis signal-regulating kinase 1
Species: mouse
Products:     Map3k5

Top Publications

  1. Tobiume K, Inage T, Takeda K, Enomoto S, Miyazono K, Ichijo H. Molecular cloning and characterization of the mouse apoptosis signal-regulating kinase 1. Biochem Biophys Res Commun. 1997;239:905-10 pubmed
    ..The overall amino acid sequence identity between the mouse and the human ASK1 was 91.9%...
  2. Tobiume K, Matsuzawa A, Takahashi T, Nishitoh H, Morita K, Takeda K, et al. ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep. 2001;2:222-8 pubmed
    ..Here we show that by deleting ASK1 in mice, TNF- and H(2)O(2)-induced sustained activations of JNK and p38 are lost in ASK1(-/-) embryonic fibroblasts,..
  3. Izumiya Y, Kim S, Izumi Y, Yoshida K, Yoshiyama M, Matsuzawa A, et al. Apoptosis signal-regulating kinase 1 plays a pivotal role in angiotensin II-induced cardiac hypertrophy and remodeling. Circ Res. 2003;93:874-83 pubmed
    ..Apoptosis signal-regulating kinase 1 (ASK1), one of mitogen-activated protein kinase kinase kinases, plays a key role in stress-induced cellular responses...
  4. Chiang E, Dang O, Anderson K, Matsuzawa A, Ichijo H, David M. Cutting edge: apoptosis-regulating signal kinase 1 is required for reactive oxygen species-mediated activation of IFN regulatory factor 3 by lipopolysaccharide. J Immunol. 2006;176:5720-4 pubmed
    ..b>ASK1 kinase activity proved essential for IRF3-mediated ISG induction by LPS...
  5. Takenouchi T, Setoguchi T, Yone K, Komiya S. Expression of apoptosis signal-regulating kinase 1 in mouse spinal cord under chronic mechanical compression: possible involvement of the stress-activated mitogen-activated protein kinase pathways in spinal cord cell apoptosis. Spine (Phila Pa 1976). 2008;33:1943-50 pubmed publisher
    ..To examine apoptosis signal cascade in neurons and oligodendrocytes under the chronic spinal cord compression of tiptoe-walking Yoshimura (TWY) mouse, which is model of progressive cervical cord compression...
  6. Kim H, Cho K, Lee S, Kim G. Apoptosis signal-regulating kinase 1 (Ask1) targeted small interfering RNA on ischemic neuronal cell death. Brain Res. 2011;1412:73-8 pubmed publisher
    Apoptosis signal-regulating kinase 1 (Ask1) is one of mitogen-activated protein kinase kinase kinase (MAPKKK) for cell differentiation and apoptosis...
  7. Kim A, Khursigara G, Sun X, Franke T, Chao M. Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol Cell Biol. 2001;21:893-901 pubmed
    ..Here we describe a novel functional interaction between Akt and apoptosis signal-regulating kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase...
  8. Nishitoh H, Kadowaki H, Nagai A, Maruyama T, Yokota T, Fukutomi H, et al. ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1. Genes Dev. 2008;22:1451-64 pubmed publisher
    ..SOD1(mut)-induced ER stress activated the apoptosis signal-regulating kinase 1 (ASK1)-dependent cell death pathway...
  9. Chang H, Nishitoh H, Yang X, Ichijo H, Baltimore D. Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx. Science. 1998;281:1860-3 pubmed
    ..Daxx was found to activate the JNK kinase kinase ASK1, and overexpression of a kinase-deficient ASK1 mutant inhibited Fas- and Daxx-induced apoptosis and JNK activation...

More Information

Publications90

  1. Kumakura K, Nomura H, Toyoda T, Hashikawa K, Noguchi T, Takeda K, et al. Hyperactivity in novel environment with increased dopamine and impaired novelty preference in apoptosis signal-regulating kinase 1 (ASK1)-deficient mice. Neurosci Res. 2010;66:313-20 pubmed publisher
    Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein (MAP) kinase kinase kinase family member, which induces apoptosis in various cells through JNK and p38 MAP kinase cascades...
  2. Harada C, Nakamura K, Namekata K, Okumura A, Mitamura Y, Iizuka Y, et al. Role of apoptosis signal-regulating kinase 1 in stress-induced neural cell apoptosis in vivo. Am J Pathol. 2006;168:261-9 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in oxidative stress-induced apoptosis...
  3. Matsuzawa A, Nishitoh H, Tobiume K, Takeda K, Ichijo H. Physiological roles of ASK1-mediated signal transduction in oxidative stress- and endoplasmic reticulum stress-induced apoptosis: advanced findings from ASK1 knockout mice. Antioxid Redox Signal. 2002;4:415-25 pubmed
    ..Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein (MAP) kinase kinase kinase family, which activates both the MKK4/MKK7-..
  4. Zhou J, Shao Z, Kerkela R, Ichijo H, Muslin A, Pombo C, et al. Serine 58 of 14-3-3zeta is a molecular switch regulating ASK1 and oxidant stress-induced cell death. Mol Cell Biol. 2009;29:4167-76 pubmed publisher
    Oxidant stress is a ubiquitous stressor with negative impacts on multiple cell types. ASK1 is a central mediator of oxidant injury, but while mechanisms of its inhibition, such as sequestration by 14-3-3 proteins and thioredoxin, have ..
  5. Cho K, Lee B, Cheon S, Kim H, Kim H, Kim G. Inhibition of apoptosis signal-regulating kinase 1 reduces endoplasmic reticulum stress and nuclear huntingtin fragments in a mouse model of Huntington disease. Neuroscience. 2009;163:1128-34 pubmed publisher
    ..In this study, we investigated the role of apoptosis signal-regulating kinase 1 (Ask1) in the pathogenesis of HD...
  6. Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 2002;16:1345-55 pubmed
    ..polyQ with pathogenic repeat length triggers ER stress through proteasomal dysfunction; (2) ER stress activates ASK 1 through formation of an IRE1-TRAF2-ASK1 complex; and (3) ASK1(-/-) primary neurons are defective in polyQ-, ..
  7. Hsieh C, Papaconstantinou J. Thioredoxin-ASK1 complex levels regulate ROS-mediated p38 MAPK pathway activity in livers of aged and long-lived Snell dwarf mice. FASEB J. 2006;20:259-68 pubmed
    ..ROS, in response to rotenone (ROT) treatment, is based on the ability of reduced Trx to bind to and inhibit ASK 1 and its release from the complex upon oxidation. This balance of free vs...
  8. Yamaguchi O, Higuchi Y, Hirotani S, Kashiwase K, Nakayama H, Hikoso S, et al. Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling. Proc Natl Acad Sci U S A. 2003;100:15883-8 pubmed
    ..The molecular mechanism of this process, however, remains to be elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis...
  9. Iriyama T, Takeda K, Nakamura H, Morimoto Y, Kuroiwa T, Mizukami J, et al. ASK1 and ASK2 differentially regulate the counteracting roles of apoptosis and inflammation in tumorigenesis. EMBO J. 2009;28:843-53 pubmed publisher
    ..Here, we show that stress-activated MAP3Ks, ASK1 and ASK2, which are involved in cellular responses to various stressors such as reactive oxygen species, ..
  10. Takeda K, Shimozono R, Noguchi T, Umeda T, Morimoto Y, Naguro I, et al. Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1. J Biol Chem. 2007;282:7522-31 pubmed
    ..Here we show that ASK2, a highly related serine/threonine kinase to ASK1, also functions as a MAP3K only in a heteromeric complex with ASK1...
  11. Yamaguchi K, Takeda K, Kadowaki H, Ueda I, Namba Y, Ouchi Y, et al. Involvement of ASK1-p38 pathway in the pathogenesis of diabetes triggered by pancreatic ß cell exhaustion. Biochim Biophys Acta. 2013;1830:3656-63 pubmed publisher
    ..p38 inhibitor (SB203580), MIN6 cell (pancreatic ß cell line), Akita mice and apoptosis signal-regulating kinase 1 (ASK1) knockout mice. The expression of Ins(C96Y) activated the ASK1-p38 pathway...
  12. Matsuzawa A, Saegusa K, Noguchi T, Sadamitsu C, Nishitoh H, Nagai S, et al. ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required for TLR4-mediated innate immunity. Nat Immunol. 2005;6:587-92 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein 3-kinase that activates both Jnk and p38 mitogen-activated protein kinases...
  13. Yamaguchi O, Watanabe T, Nishida K, Kashiwase K, Higuchi Y, Takeda T, et al. Cardiac-specific disruption of the c-raf-1 gene induces cardiac dysfunction and apoptosis. J Clin Invest. 2004;114:937-43 pubmed
    ..activation of MEK1/2 or ERK showed no difference, but the kinase activity of apoptosis signal-regulating kinase 1 (ASK1), JNK, or p38 increased significantly compared with that in controls...
  14. Kwon J, Kim E, Choi E. Stabilization of the survival motor neuron protein by ASK1. FEBS Lett. 2011;585:1287-92 pubmed publisher
    ..Here, we show that apoptosis signal-regulating kinase 1 (ASK1) stabilizes SMN protein by inhibiting SMN poly-ubiquitination, and that the kinase activity of ASK1 is less ..
  15. Huang Y, Wu L, Wu J, Li Y, Hou L. Cellular FLICE-like inhibitory protein protects against cardiac hypertrophy by blocking ASK1/p38 signaling in mice. Mol Cell Biochem. 2014;397:87-95 pubmed publisher
    ..Western blot experiments further showed Flip knockout activated markedly ASK1/P38 signaling cascades in vivo and in vitro...
  16. Hsieh C, Kuro O M, Rosenblatt K, Brobey R, Papaconstantinou J. The ASK1-Signalosome regulates p38 MAPK activity in response to levels of endogenous oxidative stress in the Klotho mouse models of aging. Aging (Albany NY). 2010;2:597-611 pubmed
    ..mice (low ROS and resistance to ROS) to determine whether the ROS-sensitive apoptosis signal-regulating kinase (ASK1)-signalosome -> p38 MAPK pathway plays a role in the accelerated aging of Klotho(-/-), and resistance to ..
  17. Zhang R, Luo D, Miao R, Bai L, Ge Q, Sessa W, et al. Hsp90-Akt phosphorylates ASK1 and inhibits ASK1-mediated apoptosis. Oncogene. 2005;24:3954-63 pubmed
    Hsp90 client protein Akt has been shown to inhibit cell apoptosis in part by inhibiting proapoptotic kinase ASK1 (apoptosis signal-regulating kinase 1) activity...
  18. Kundu M, Pathak S, Kumawat K, Basu S, Chatterjee G, Pathak S, et al. A TNF- and c-Cbl-dependent FLIP(S)-degradation pathway and its function in Mycobacterium tuberculosis-induced macrophage apoptosis. Nat Immunol. 2009;10:918-26 pubmed publisher
    ..TNF activated a pathway involving the kinases ASK1, p38 and c-Abl...
  19. Azuchi Y, Kimura A, Guo X, Akiyama G, Noro T, Harada C, et al. Valproic acid and ASK1 deficiency ameliorate optic neuritis and neurodegeneration in an animal model of multiple sclerosis. Neurosci Lett. 2017;639:82-87 pubmed publisher
    ..We also examined the effects of apoptosis signal-regulating kinase 1 (ASK1), an evolutionarily conserved signaling intermediate for innate immunity, in EAE mice...
  20. Vauzour D, Pinto J, Cooper A, Spencer J. The neurotoxicity of 5-S-cysteinyldopamine is mediated by the early activation of ERK1/2 followed by the subsequent activation of ASK1/JNK1/2 pro-apoptotic signalling. Biochem J. 2014;463:41-52 pubmed publisher
    ..Our data suggest a novel comprehensive mechanism for CysDA that may hold relevance for the selective neuronal loss observed in Parkinson's disease. ..
  21. Cheon S, Cho K, Song J, Kim G. Knockdown of apoptosis signal-regulating kinase 1 affects ischaemia-induced astrocyte activation and glial scar formation. Eur J Neurosci. 2016;43:912-22 pubmed publisher
    ..Apoptosis signal-regulating kinase 1 (ASK1) is an early responder to oxidative stress, and plays a pivotal role in the intracellular signalling pathway of ..
  22. Im J, Lee K, Junn E, Mouradian M. DJ-1 protects against oxidative damage by regulating the thioredoxin/ASK1 complex. Neurosci Res. 2010;67:203-8 pubmed publisher
    ..A key effector of oxidant-induced cell death is the MAP3 kinase apoptosis signal-regulating kinase 1 (ASK1) which is bound to and inhibited by thioredoxin 1 (Trx1) under basal conditions...
  23. Sekimukai D, Honda S, Negi A. RNA interference for apoptosis signal-regulating kinase-1 (ASK-1) rescues photoreceptor death in the rd1 mouse. Mol Vis. 2009;15:1764-73 pubmed
    To evaluate whether RNA interference against apoptosis signal-regulating kinase-1 (ASK-1), a gene involved in stress-induced apoptosis, inhibits photoreceptor death in retinal degeneration 1 (rd1) mice...
  24. Toyama K, Koibuchi N, Hasegawa Y, Uekawa K, Yasuda O, Sueta D, et al. ASK1 is involved in cognitive impairment caused by long-term high-fat diet feeding in mice. Sci Rep. 2015;5:10844 pubmed publisher
    ..We have previously shown that apoptosis signal-regulating kinase 1 (ASK1) is responsible for cognitive impairment caused by chronic cerebral hypoperfusion...
  25. Harada C, Namekata K, Guo X, Yoshida H, Mitamura Y, Matsumoto Y, et al. ASK1 deficiency attenuates neural cell death in GLAST-deficient mice, a model of normal tension glaucoma. Cell Death Differ. 2010;17:1751-9 pubmed publisher
    Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase and has an important role in stress-induced retinal ganglion cell (RGC) apoptosis...
  26. Park H, Cho S, Kim C, Hwang H, Noh K, Kim M, et al. Heat shock protein hsp72 is a negative regulator of apoptosis signal-regulating kinase 1. Mol Cell Biol. 2002;22:7721-30 pubmed
    ..C for 20 min) resulted in inhibition of H(2)O(2)-induced activation of apoptosis signal-regulating kinase 1 (ASK1)...
  27. Jung H, Seong H, Ha H. Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation. J Biol Chem. 2008;283:34541-53 pubmed publisher
    ..Here we demonstrate a functional association between MPK38 and apoptosis signal-regulating kinase 1 (ASK1)...
  28. Tran P, Ho S, Kim B, Vuong T, Leem Y, Bae G, et al. TGF-?-activated kinase 1 (TAK1) and apoptosis signal-regulating kinase 1 (ASK1) interact with the promyogenic receptor Cdo to promote myogenic differentiation via activation of p38MAPK pathway. J Biol Chem. 2012;287:11602-15 pubmed publisher
    ..Two MAP3Ks, TAK1 and ASK1, can activate p38MAPK via MKK6 in various cell systems...
  29. Kataoka K, Tokutomi Y, Yamamoto E, Nakamura T, Fukuda M, Dong Y, et al. Apoptosis signal-regulating kinase 1 deficiency eliminates cardiovascular injuries induced by high-salt diet. J Hypertens. 2011;29:76-84 pubmed publisher
    ..Wild-type and ASK1-/- mice were fed a low-salt or a high-salt diet for 10 weeks and the effects of high-salt diet on food intake, ..
  30. Seong H, Jung H, Ichijo H, Ha H. Reciprocal negative regulation of PDK1 and ASK1 signaling by direct interaction and phosphorylation. J Biol Chem. 2010;285:2397-414 pubmed publisher
    ..association between PDK1 (3-phosphoinositide-dependent protein kinase 1), a critical mediator of cell survival, and ASK1 (apoptosis signal-regulating kinase 1), an apoptotic stress-activated MAPKKK...
  31. Wu Y, Zhang S, Kim Y, Tan H, Whiteman M, Ong C, et al. Signaling pathways from membrane lipid rafts to JNK1 activation in reactive nitrogen species-induced non-apoptotic cell death. Cell Death Differ. 2008;15:386-97 pubmed
    ..we identified tumor necrosis factor receptor-associated factor 2 (TRAF2) and apoptosis signal-regulating kinase 1 (ASK1) as the essential upstream molecules for RNS-induced JNK activation and cell death...
  32. Yang P, Li X, Xu C, Eckert R, Reece E, Zielke H, et al. Maternal hyperglycemia activates an ASK1-FoxO3a-caspase 8 pathway that leads to embryonic neural tube defects. Sci Signal. 2013;6:ra74 pubmed publisher
    ..We demonstrated that maternal hyperglycemia correlated with activation of the apoptosis signal-regulating kinase 1 (ASK1) in the developing neural tube, and Ask1 gene deletion was associated with reduced neuroepithelial cell apoptosis ..
  33. Takada E, Furuhata M, Nakae S, Ichijo H, Sudo K, Mizuguchi J. Requirement of apoptosis-inducing kinase 1 for the induction of bronchial asthma following stimulation with ovalbumin. Int Arch Allergy Immunol. 2013;162:104-14 pubmed publisher
    Bronchial asthma is a chronic inflammatory disease of the airway. Apoptosis signal-regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase kinase kinase family, is activated by environmental stress and plays a crucial ..
  34. Zhang Q, Eaton G, Diallo C, Freeman T. Stress-Induced Activation of Apoptosis Signal-Regulating Kinase 1 Promotes Osteoarthritis. J Cell Physiol. 2016;231:944-53 pubmed publisher
    Apoptosis signal-regulated kinase 1 (ASK1) has been shown to affect a wide range of cellular processes including stress-related responses, cytokine and growth factor signaling, cell cycle and cell death...
  35. Makena P, Gorantla V, Ghosh M, Bezawada L, Kandasamy K, Balazs L, et al. Deletion of apoptosis signal-regulating kinase-1 prevents ventilator-induced lung injury in mice. Am J Respir Cell Mol Biol. 2012;46:461-9 pubmed publisher
    ..In this study, we hypothesized that apoptosis signal-regulating kinase-1 (ASK-1), a redox-sensitive, mitogen-activated protein kinase kinase kinase, plays a role in lung injury and apoptosis in ..
  36. Furuhata M, Takada E, Noguchi T, Ichijo H, Mizuguchi J. Apoptosis signal-regulating kinase (ASK)-1 mediates apoptosis through activation of JNK1 following engagement of membrane immunoglobulin. Exp Cell Res. 2009;315:3467-76 pubmed publisher
    ..In this study, we show that apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase 1 (JNK1) signaling pathway participates in mIg-induced apoptosis through the generation of ..
  37. Song J, Cho K, Cheon S, Kim S, Park K, Lee W, et al. Apoptosis signal-regulating kinase 1 (ASK1) is linked to neural stem cell differentiation after ischemic brain injury. Exp Mol Med. 2013;45:e69 pubmed publisher
    ..Apoptosis signal-regulating kinase 1 (ASK1) is preferentially activated by oxidative stress and inflammation, which is the fundamental pathology of brain ..
  38. Görner K, Holtorf E, Waak J, Pham T, Vogt Weisenhorn D, Wurst W, et al. Structural determinants of the C-terminal helix-kink-helix motif essential for protein stability and survival promoting activity of DJ-1. J Biol Chem. 2007;282:13680-91 pubmed
  39. Izumi Y, Kim Mitsuyama S, Yoshiyama M, Omura T, Shiota M, Matsuzawa A, et al. Important role of apoptosis signal-regulating kinase 1 in ischemia-induced angiogenesis. Arterioscler Thromb Vasc Biol. 2005;25:1877-83 pubmed
    We first examined the role of apoptosis signal-regulating kinase 1 (ASK1), one of mitogen-activated protein kinase kinase kinases, in ischemia-induced angiogenesis...
  40. Park H, Yu J, Cho J, Kim M, Huh S, Ryoo K, et al. Inhibition of apoptosis signal-regulating kinase 1 by nitric oxide through a thiol redox mechanism. J Biol Chem. 2004;279:7584-90 pubmed
    ..NO has now been shown to inhibit the activation of apoptosis signal-regulating kinase 1 (ASK1) in murine fibrosarcoma L929 cells through such a mechanism...
  41. Cho J, Lee J, Lee E, Nam D, Shim B, Song M, et al. 8?-hydroxy-3-oxopimar-15-ene exerts anti-inflammatory effects by inhibiting ROS-mediated activation of the TRAF6-ASK1-p38 signaling pathway. Immunopharmacol Immunotoxicol. 2013;35:549-57 pubmed publisher
    ..Therefore, we demonstrate here that OXO can potentially inhibit several biomarkers related to inflammation through inhibition of ROS-mediated activation of TRAF6-ASK1-p38 pathway.
  42. Kim S, Shim J, Chun E, Lee K. Reciprocal inhibition between the transforming growth factor-?-activated kinase 1 (TAK1) and apoptosis signal-regulating kinase 1 (ASK1) mitogen-activated protein kinase kinase kinases and its suppression by TAK1-binding protein 2 (TAB2), an adapter . J Biol Chem. 2012;287:3381-91 pubmed publisher
    ..transforming growth factor-?-activated kinase 1 (TAK1)-TAK1-binding protein 1 (TAB1) complex negatively regulates ASK1-mediated signaling, and TAB2 reciprocally regulates TAK1-induced NF-?B and apoptosis signal-regulating kinase 1 (..
  43. Cho K, Kim H, Cheon S, Lee J, Kim G. Apoptosis signal-regulating kinase-1 aggravates ROS-mediated striatal degeneration in 3-nitropropionic acid-infused mice. Biochem Biophys Res Commun. 2013;441:280-5 pubmed publisher
    Apoptosis signal-regulating kinase-1 (ASK1), an early signaling element in the cell death pathway, has been suggested to participate in the pathology of neurodegenerative diseases, which may be associated with environmental factors that ..
  44. Liu H, Xu R, Feng L, Guo W, Cao N, Qian C, et al. A novel chromone derivative with anti-inflammatory property via inhibition of ROS-dependent activation of TRAF6-ASK1-p38 pathway. PLoS ONE. 2012;7:e37168 pubmed publisher
    ..reactive oxygen species (ROS) was remarkably impaired by DCO-6, which disrupted the formation of the TRAF6-ASK1 complex...
  45. Yokoi T, Fukuo K, Yasuda O, Hotta M, Miyazaki J, Takemura Y, et al. Apoptosis signal-regulating kinase 1 mediates cellular senescence induced by high glucose in endothelial cells. Diabetes. 2006;55:1660-5 pubmed
    ..Here, we show that high glucose induces activation of apoptosis signal-regulating kinase 1 (ASK1), an apoptosis-inducing signal that mediates endothelial cell senescence induced by hyperglycemia...
  46. Yu L, Min W, He Y, Qin L, Zhang H, Bennett A, et al. JAK2 and SHP2 reciprocally regulate tyrosine phosphorylation and stability of proapoptotic protein ASK1. J Biol Chem. 2009;284:13481-8 pubmed publisher
    Previously we have shown that tyrosine 718 of ASK1 when phosphorylated is critical for SOCS1 binding and SOCS1-mediated degradation of ASK1...
  47. Adekeye A, Haeri M, Solessio E, Knox B. Ablation of the proapoptotic genes CHOP or Ask1 does not prevent or delay loss of visual function in a P23H transgenic mouse model of retinitis pigmentosa. PLoS ONE. 2014;9:e83871 pubmed publisher
    ..We examined the role of the ER stress proteins, Chop and Ask1, in regulating the death of rod photoreceptors in a mouse line harboring the Rho(P23H) rhodopsin transgene (GHL(+))...
  48. Noguchi H, Yamada S, Nabeshima A, Guo X, Tanimoto A, Wang K, et al. Depletion of apoptosis signal-regulating kinase 1 prevents bile duct ligation-induced necroinflammation and subsequent peribiliary fibrosis. Am J Pathol. 2014;184:644-61 pubmed publisher
    Apoptosis signal-regulating kinase 1 (ASK1), also known as mitogen-activated protein kinase kinase kinase (MAP3K), is ubiquitously expressed and situated in an important upstream position of many signal transduction pathways...
  49. Nakagawa H, Hirata Y, Takeda K, Hayakawa Y, Sato T, Kinoshita H, et al. Apoptosis signal-regulating kinase 1 inhibits hepatocarcinogenesis by controlling the tumor-suppressing function of stress-activated mitogen-activated protein kinase. Hepatology. 2011;54:185-95 pubmed publisher
    ..We investigated the role of apoptosis signal-regulating kinase 1 (ASK1), a major player in the regulation of JNK and p38 activities, in hepatocarcinogenesis using a mouse hepatocellular ..
  50. Gan B, Peng X, Nagy T, Alcaraz A, Gu H, Guan J. Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways. J Cell Biol. 2006;175:121-33 pubmed
    ..TNF) alpha stimulation, which might be mediated by FIP200 interaction with apoptosis signal-regulating kinase 1 (ASK1) and TNF receptor-associated factor 2 (TRAF2), regulation of TRAF2-ASK1 interaction, and ASK1 phosphorylation...
  51. Yamada S, Ding Y, Tanimoto A, Wang K, Guo X, Li Z, et al. Apoptosis signal-regulating kinase 1 deficiency accelerates hyperlipidemia-induced atheromatous plaques via suppression of macrophage apoptosis. Arterioscler Thromb Vasc Biol. 2011;31:1555-64 pubmed publisher
    ..Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays a pivotal role in stress-induced apoptosis...
  52. Ebrahimian T, Sairam M, Schiffrin E, Touyz R. Cardiac hypertrophy is associated with altered thioredoxin and ASK-1 signaling in a mouse model of menopause. Am J Physiol Heart Circ Physiol. 2008;295:H1481-8 pubmed publisher
    ..endogenous antioxidant that also interacts with signaling molecules, such as apoptosis signal-regulated kinase 1 (ASK-1), independently of its antioxidant function...
  53. Hayakawa Y, Hirata Y, Nakagawa H, Sakamoto K, Hikiba Y, Kinoshita H, et al. Apoptosis signal-regulating kinase 1 and cyclin D1 compose a positive feedback loop contributing to tumor growth in gastric cancer. Proc Natl Acad Sci U S A. 2011;108:780-5 pubmed publisher
    ..Apoptosis signal-regulating kinase 1 (ASK1) is an upstream MAPK involved in apoptosis, inflammation, and carcinogenesis...
  54. Kim I, Shu C, Xu W, Shiau C, Grant D, Vasile S, et al. Chemical biology investigation of cell death pathways activated by endoplasmic reticulum stress reveals cytoprotective modulators of ASK1. J Biol Chem. 2009;284:1593-603 pubmed publisher
    ..Active benzodiazepinones suppressed cell death at the level of apoptotic signal kinase-1 (ASK1) within the IRE1 pathway but without directly inhibiting the kinase activity of ASK1 or >400 other kinases ..
  55. Huang Q, Zhou H, Zhang H, Huang Y, Hinojosa Kirschenbaum F, Fan P, et al. Thioredoxin-2 inhibits mitochondrial reactive oxygen species generation and apoptosis stress kinase-1 activity to maintain cardiac function. Circulation. 2015;131:1082-97 pubmed publisher
    ..by suppressing mitochondrial reactive oxygen species generation and by inhibiting apoptosis stress kinase-1 (ASK1)-dependent apoptotic signaling...
  56. Ferrer Vaquer A, Maurey P, Firnberg N, Leibbrandt A, Neubüser A. Expression of ASK1 during chick and early mouse development. Gene Expr Patterns. 2007;7:808-16 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is an important regulator of stress-induced cell death...
  57. Yu Z, Chen T, Li X, Yang M, Tang S, Zhu X, et al. Lys29-linkage of ASK1 by Skp1-Cullin 1-Fbxo21 ubiquitin ligase complex is required for antiviral innate response. elife. 2016;5: pubmed publisher
    ..unknown component of SCF (Skp1-Cul1-F-box protein) complex, facilitates Lys29-linkage and activation of ASK1 (apoptosis signal-regulating kinase 1), and promotes type I interferon production upon viral infection...
  58. Brobey R, GERMAN D, Sonsalla P, Gurnani P, Pastor J, Hsieh C, et al. Klotho Protects Dopaminergic Neuron Oxidant-Induced Degeneration by Modulating ASK1 and p38 MAPK Signaling Pathways. PLoS ONE. 2015;10:e0139914 pubmed publisher
    ..we tested the hypothesis that the reactive oxygen species (ROS)-sensitive apoptosis signal-regulating kinase 1 (ASK1)/p38 MAPK pathway regulates stress levels in the brain of these mice and showed that: 1) the ratio of free ASK1 to ..
  59. Toyama K, Koibuchi N, Uekawa K, Hasegawa Y, Kataoka K, Katayama T, et al. Apoptosis signal-regulating kinase 1 is a novel target molecule for cognitive impairment induced by chronic cerebral hypoperfusion. Arterioscler Thromb Vasc Biol. 2014;34:616-25 pubmed publisher
    ..We investigated whether apoptosis signal-regulating kinase 1 (ASK1) might be a key molecule in cerebral hypoperfusion, associated with blood-brain barrier breakdown and white matter ..
  60. Newton V, Ali S, Duddy G, Whitmarsh A, Gardiner N. Targeting apoptosis signalling kinase-1 (ASK-1) does not prevent the development of neuropathy in streptozotocin-induced diabetic mice. PLoS ONE. 2014;9:e107437 pubmed publisher
    Apoptosis signal-regulating kinase-1 (ASK1) is a mitogen-activated protein 3 kinase (MAPKKK/MAP3K) which lies upstream of the stress-activated MAPKs, JNK and p38...
  61. Ma F, Tesch G, Nikolic Paterson D. ASK1/p38 signaling in renal tubular epithelial cells promotes renal fibrosis in the mouse obstructed kidney. Am J Physiol Renal Physiol. 2014;307:F1263-73 pubmed publisher
    ..Apoptosis signal-regulating kinase 1 (ASK1/MAPKKK5) is a member of the MAPKKK family that can induce activation of p38 and JNK...
  62. Zhang Q, Kurpad D, Mahoney M, Steinbeck M, Freeman T. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration. PLoS ONE. 2017;12:e0185803 pubmed publisher
    ..of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes ..
  63. Watanabe T, Otsu K, Takeda T, Yamaguchi O, Hikoso S, Kashiwase K, et al. Apoptosis signal-regulating kinase 1 is involved not only in apoptosis but also in non-apoptotic cardiomyocyte death. Biochem Biophys Res Commun. 2005;333:562-7 pubmed
    ..Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis...
  64. Hayakawa Y, Hirata Y, Nakagawa H, Sakamoto K, Hikiba Y, Otsuka M, et al. Apoptosis signal-regulating kinase 1 regulates colitis and colitis-associated tumorigenesis by the innate immune responses. Gastroenterology. 2010;138:1055-67.e1-4 pubmed publisher
    ..Apoptosis signal-regulating kinase 1 (ASK1) is a MAPK kinase kinase; little is known about the role of ASK1 in colonic disease...
  65. Hsu M, Chang C, Chen M, Chen B, Ma H, Hong C, et al. Apoptosis signal-regulating kinase 1 in peptidoglycan-induced COX-2 expression in macrophages. J Leukoc Biol. 2010;87:1069-82 pubmed publisher
    In this study, we investigated the role of ASK1 in PGN-induced C/EBPbeta activation and COX-2 expression in RAW 264.7 macrophages...
  66. Pepin E, Higa A, Schuster Klein C, Bernard C, Sulpice T, Guardiola B, et al. Deletion of apoptosis signal-regulating kinase 1 (ASK1) protects pancreatic beta-cells from stress-induced death but not from glucose homeostasis alterations under pro-inflammatory conditions. PLoS ONE. 2014;9:e112714 pubmed publisher
    ..Recent observations suggest that apoptosis signal-regulating kinase 1 (ASK1) is involved in beta-cell death in response to different stressors...
  67. Hsu M, Hsu C, Chen B, Chen M, Ou G, Lin C. Apoptosis signal-regulating kinase 1 in amyloid beta peptide-induced cerebral endothelial cell apoptosis. J Neurosci. 2007;27:5719-29 pubmed
    ..We explore the role of apoptosis signal-regulating kinase 1 (ASK1) in Abeta-induced death in primary cultures of murine CECs...
  68. Gerits N, Kostenko S, Moens U. In vivo functions of mitogen-activated protein kinases: conclusions from knock-in and knock-out mice. Transgenic Res. 2007;16:281-314 pubmed
    ..Moreover, examples of the application of MAP kinase transgenic mice for validating therapeutic properties of specific MAP kinase inhibitors, and for investigating the role of MAP kinase in pathogen-host interactions will be discussed. ..
  69. Wang F, Wu Y, Gu H, Reece E, Fang S, Gabbay Benziv R, et al. Ask1 gene deletion blocks maternal diabetes-induced endoplasmic reticulum stress in the developing embryo by disrupting the unfolded protein response signalosome. Diabetes. 2015;64:973-88 pubmed publisher
    Apoptosis signal-regulating kinase 1 (ASK1) is activated by various stresses. The link between ASK1 activation and endoplasmic reticulum (ER) stress, two causal events in diabetic embryopathy, has not been determined...
  70. Lin F, Huang S, Hung K, Su S, Chung C, Matsuzawa A, et al. ASK1 promotes apoptosis of normal and malignant plasma cells. Blood. 2012;120:1039-47 pubmed publisher
    ..Here, we show that apoptosis signal-regulating kinase 1 (ASK1) contributes to apoptosis of plasma cells because ASK1 activity was induced during differentiation of short-lived ..
  71. Fan G, Yuan Q, Song G, Wang Y, Chen G, Qian J, et al. Small heat-shock protein Hsp20 attenuates beta-agonist-mediated cardiac remodeling through apoptosis signal-regulating kinase 1. Circ Res. 2006;99:1233-42 pubmed
    ..These beneficial effects were associated with attenuation of the ASK1-JNK/p38 (apoptosis signal-regulating kinase 1/c-Jun NH(2)-terminal kinase/p38) signaling cascade triggered by ..
  72. Um J, Im E, Park J, Oh Y, Min B, Lee H, et al. ASK1 negatively regulates the 26 S proteasome. J Biol Chem. 2010;285:36434-46 pubmed publisher
    ..Here, cell culture experiments and in vitro assays demonstrated that apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPK kinase kinase family, negatively regulated 26 S proteasome activity...
  73. Manoharan R, Seong H, Ha H. Thioredoxin inhibits MPK38-induced ASK1, TGF-?, and p53 function in a phosphorylation-dependent manner. Free Radic Biol Med. 2013;63:313-24 pubmed publisher
    ..Expression of wild-type Trx, but not the Trx mutants C32S/C35S and T76A, inhibited MPK38-induced ASK1, TGF-?, and p53 function by destabilizing MPK38...
  74. Eaton G, Zhang Q, Diallo C, Matsuzawa A, Ichijo H, Steinbeck M, et al. Inhibition of apoptosis signal-regulating kinase 1 enhances endochondral bone formation by increasing chondrocyte survival. Cell Death Dis. 2014;5:e1522 pubmed publisher
    ..Apoptosis Signal-Regulating Kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK), which is activated by reactive oxygen species and other cellular ..
  75. Osaka N, Takahashi T, Murakami S, Matsuzawa A, Noguchi T, Fujiwara T, et al. ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds. J Cell Biol. 2007;176:903-9 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein 3-kinase family that activates both c-Jun NH(2)-terminal kinase and p38 pathways in response to inflammatory cytokines and physicochemical stress...
  76. Gade P, Manjegowda S, Nallar S, Maachani U, Cross A, Kalvakolanu D. Regulation of the death-associated protein kinase 1 expression and autophagy via ATF6 requires apoptosis signal-regulating kinase 1. Mol Cell Biol. 2014;34:4033-48 pubmed publisher
    ..Here, we report that IFN-? activates the ASK1-MKK3/MKK6-p38 mitogen-activated protein kinase (MAPK) pathway for controlling the activity of ATF6...
  77. Bijangi Vishehsaraei K, Saadatzadeh M, Werne A, McKenzie K, Kapur R, Ichijo H, et al. Enhanced TNF-alpha-induced apoptosis in Fanconi anemia type C-deficient cells is dependent on apoptosis signal-regulating kinase 1. Blood. 2005;106:4124-30 pubmed
    ..oxidant-induced apoptotic signaling through the redox-dependent protein, apoptosis signal-regulating kinase 1 (Ask1)...
  78. Li W, Xiong Y, Shang C, Twu K, Hang C, Yang J, et al. Brg1 governs distinct pathways to direct multiple aspects of mammalian neural crest cell development. Proc Natl Acad Sci U S A. 2013;110:1738-43 pubmed publisher
    ..Brg1 suppresses an apoptosis factor, Apoptosis signal-regulating kinase 1 (Ask1), and a cell cycle inhibitor, p21(cip1), to inhibit apoptosis and promote proliferation of NCCs, thereby ..
  79. Nakamura T, Kataoka K, Fukuda M, Nako H, Tokutomi Y, Dong Y, et al. Critical role of apoptosis signal-regulating kinase 1 in aldosterone/salt-induced cardiac inflammation and fibrosis. Hypertension. 2009;54:544-51 pubmed publisher
    ..This work was undertaken to determine the role of apoptosis signal-regulating kinase 1 (ASK1) in the mechanism underlying aldosterone-induced cardiac injury in vivo...
  80. Yuk J, Shin D, Yang C, Kim K, An S, Rho J, et al. Role of apoptosis-regulating signal kinase 1 in innate immune responses by Mycobacterium bovis bacillus Calmette-Guérin. Immunol Cell Biol. 2009;87:100-7 pubmed publisher
    ..M. bovis BCG-induced ROS production led to robust activation of ASK1 upstream of the c-jun-N-terminal kinase and p38 MAPK, but not extracellular-regulated kinase 1/2...
  81. Katome T, Namekata K, Guo X, Semba K, Kittaka D, Kawamura K, et al. Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury. Cell Death Differ. 2013;20:270-80 pubmed publisher
    ..Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase and has an important role in ..