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Mitogen-activated protein kinase kinase kinase 5

PDB rendering based on 2clq.
Available structures
2clq
Identifiers
Symbols MAP3K5; ASK1; MAPKKK5; MEKK5
External IDs OMIM602448 MGI1346876 HomoloGene38114 GeneCards: MAP3K5 Gene
RNA expression pattern
PBB GE MAP3K5 203837 at tn.png
PBB GE MAP3K5 203836 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4217 26408
Ensembl ENSG00000197442 n/a
UniProt Q99683 n/a
RefSeq (mRNA) NM_005923 XM_001006040
RefSeq (protein) NP_005914 XP_001006040
Location (UCSC) Chr 6:
136.92 - 137.16 Mb
n/a
PubMed search [1] [2]

Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5) is an enzyme which in humans is encoded by the MAP3K5 gene. This gene is located on chromosome 6 at locus 6q22.33[1] and the transcribed protein contains 1,374 amino acids with 11 kinase subdomains.

Contents

Function

ASK1/MAP3K5 is part of the mitogen-activated protein kinase (MAPK) cascade.

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 ASK1 protein can lead to apoptosis or other cellular responses depending on the cell type. Northern blot analysis shows that ASK1 transcript is abundantly expressed in human heart and pancreas. The ASK1 (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; ASK1 does not activate MAPK/ERK.[2]

ASK1 found in the inactive form, bound to reduced thioredoxin. When oxidized by a reactive oxygen species, Trx dissociates from ASK1. The ASK1, which is found as a homo-oligodimer, autophosphorylates and becomes an active MAP kinase kinase kinase.

Interactions

ASK1 has been shown to interact with Thioredoxin,[3][4][5] GADD45B,[6] Protein kinase R,[7] CDC25A,[8] Death associated protein 6,[9] RB1CC1,[10] HSPA1A,[11] C-Raf,[12] PDCD6,[13] TRAF2,[14][15][10] PPP5C,[4] MAPK8IP3,[16] TRAF6,[14][15][17] MAP2K6,[18][4] TRAF5,[14][15] MAP3K7[17] and DUSP19.[19]

References

  1. ^ Rampoldi L, Zimbello R, Bortoluzzi S, Tiso N, Valle G, Lanfranchi G, Danieli GA (1997). "Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5". Cytogenet. Cell Genet. 78 (3-4): 301–3. PMID 9465908.  
  2. ^ "Entrez Gene: MAP3K5 mitogen-activated protein kinase kinase kinase 5". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4217.  
  3. ^ Liu, Yingmei; Min Wang (Jun. 2002). "Thioredoxin promotes ASK1 ubiquitination and degradation to inhibit ASK1-mediated apoptosis in a redox activity-independent manner". Circ. Res. (United States) 90 (12): 1259–66. PMID 12089059.  
  4. ^ a b c Morita, K; Saitoh M, Tobiume K, Matsuura H, Enomoto S, Nishitoh H, Ichijo H (Nov. 2001). "Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress". EMBO J. (England) 20 (21): 6028–36. doi:10.1093/emboj/20.21.6028. ISSN 0261-4189. PMID 11689443.  
  5. ^ Saitoh, M; Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, Kawabata M, Miyazono K, Ichijo H (May. 1998). "Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1". EMBO J. (ENGLAND) 17 (9): 2596–606. doi:10.1093/emboj/17.9.2596. ISSN 0261-4189. PMID 9564042.  
  6. ^ Papa, Salvatore; Zazzeroni Francesca, Bubici Concetta, Jayawardena Shanthi, Alvarez Kellean, Matsuda Shuji, Nguyen Dung U, Pham Can G, Nelsbach Andreas H, Melis Tiziana, De Smaele Enrico, Tang Wei-Jen, D'Adamio Luciano, Franzoso Guido (Feb. 2004). "Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2". Nat. Cell Biol. (England) 6 (2): 146–53. doi:10.1038/ncb1093. ISSN 1465-7392. PMID 14743220.  
  7. ^ Takizawa, Takenori; Tatematsu Chizuru, Nakanishi Yoshinobu (Dec. 2002). "Double-stranded RNA-activated protein kinase interacts with apoptosis signal-regulating kinase 1. Implications for apoptosis signaling pathways". Eur. J. Biochem. (Germany) 269 (24): 6126–32. ISSN 0014-2956. PMID 12473108.  
  8. ^ Zou, X; Tsutsui T, Ray D, Blomquist J F, Ichijo H, Ucker D S, Kiyokawa H (Jul. 2001). "The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1". Mol. Cell. Biol. (United States) 21 (14): 4818–28. doi:10.1128/MCB.21.14.4818-4828.2001. ISSN 0270-7306. PMID 11416155.  
  9. ^ Chang, H Y; Nishitoh H, Yang X, Ichijo H, Baltimore D (Sep. 1998). "Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx". Science (UNITED STATES) 281 (5384): 1860–3. ISSN 0036-8075. PMID 9743501.  
  10. ^ a b Gan, Boyi; Peng Xu, Nagy Tamas, Alcaraz Ana, Gu Hua, Guan Jun-Lin (Oct. 2006). "Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways". J. Cell Biol. (United States) 175 (1): 121–33. doi:10.1083/jcb.200604129. ISSN 0021-9525. PMID 17015619.  
  11. ^ Park, Hee-Sae; Cho Ssang-Goo, Kim Chang Kyun, Hwang Hyun Sub, Noh Kyung Tae, Kim Mi-Sung, Huh Sung-Ho, Kim Myung Jin, Ryoo Kanghyun, Kim Eun Kyung, Kang Woo Jin, Lee Jae-Seon, Seo Jeong-Sun, Ko Young-Gyu, Kim Sunghoon, Choi Eui-Ju (Nov. 2002). "Heat shock protein hsp72 is a negative regulator of apoptosis signal-regulating kinase 1". Mol. Cell. Biol. (United States) 22 (22): 7721–30. ISSN 0270-7306. PMID 12391142.  
  12. ^ Chen, J; Fujii K, Zhang L, Roberts T, Fu H (Jul. 2001). "Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism". Proc. Natl. Acad. Sci. U.S.A. (United States) 98 (14): 7783–8. doi:10.1073/pnas.141224398. ISSN 0027-8424. PMID 11427728.  
  13. ^ Hwang, In-Sik; Jung Yong-Sam, Kim Eunhee (Oct. 2002). "Interaction of ALG-2 with ASK1 influences ASK1 localization and subsequent JNK activation". FEBS Lett. (Netherlands) 529 (2-3): 183–7. ISSN 0014-5793. PMID 12372597.  
  14. ^ a b c Nishitoh, H; Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, Miyazono K, Ichijo H (Sep. 1998). "ASK1 is essential for JNK/SAPK activation by TRAF2". Mol. Cell (UNITED STATES) 2 (3): 389–95. ISSN 1097-2765. PMID 9774977.  
  15. ^ a b c Hoeflich, K P; Yeh W C, Yao Z, Mak T W, Woodgett J R (Oct. 1999). "Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1)". Oncogene (ENGLAND) 18 (42): 5814–20. doi:10.1038/sj.onc.1202975. ISSN 0950-9232. PMID 10523862.  
  16. ^ Matsuura, Hiroshi; Nishitoh Hideki, Takeda Kohsuke, Matsuzawa Atsushi, Amagasa Teruo, Ito Michihiko, Yoshioka Katsuji, Ichijo Hidenori (Oct. 2002). "Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade". J. Biol. Chem. (United States) 277 (43): 40703–9. doi:10.1074/jbc.M202004200. ISSN 0021-9258. PMID 12189133.  
  17. ^ a b Mochida, Y; Takeda K, Saitoh M, Nishitoh H, Amagasa T, Ninomiya-Tsuji J, Matsumoto K, Ichijo H (Oct. 2000). "ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction". J. Biol. Chem. (UNITED STATES) 275 (42): 32747–52. doi:10.1074/jbc.M003042200. ISSN 0021-9258. PMID 10921914.  
  18. ^ Huang, Shile; Shu Lili, Dilling Michael B, Easton John, Harwood Franklin C, Ichijo Hidenori, Houghton Peter J (Jun. 2003). "Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1)". Mol. Cell (United States) 11 (6): 1491–501. ISSN 1097-2765. PMID 12820963.  
  19. ^ Zama, Takeru; Aoki Ryoko, Kamimoto Takahiro, Inoue Koichi, Ikeda Yasuo, Hagiwara Masatoshi (Jun. 2002). "Scaffold role of a mitogen-activated protein kinase phosphatase, SKRP1, for the JNK signaling pathway". J. Biol. Chem. (United States) 277 (26): 23919–26. doi:10.1074/jbc.M200838200. ISSN 0021-9258. PMID 11959862.  

Further reading

  • Hayakawa T, Matsuzawa A, Noguchi T, Takeda K, Ichijo H (2006). "The ASK1-MAP kinase pathways in immune and stress responses". Microbes Infect. 8 (4): 1098–107. doi:10.1016/j.micinf.2005.12.001. PMID 16517200.  
  • Nagai H, Noguchi T, Takeda K, Ichijo H (2007). "Pathophysiological roles of ASK1-MAP kinase signaling pathways.". J. Biochem. Mol. Biol. 40 (1): 1–6. PMID 17244475.  
  • Wang XS, Diener K, Jannuzzi D, et al. (1997). "Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase.". J. Biol. Chem. 271 (49): 31607–11. PMID 8940179.  
  • Ichijo H, Nishida E, Irie K, et al. (1997). "Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways.". Science 275 (5296): 90–4. PMID 8974401.  
  • Rampoldi L, Zimbello R, Bortoluzzi S, et al. (1998). "Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5.". Cytogenet. Cell Genet. 78 (3-4): 301–3. PMID 9465908.  
  • Saitoh M, Nishitoh H, Fujii M, et al. (1998). "Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1.". EMBO J. 17 (9): 2596–606. doi:10.1093/emboj/17.9.2596. PMID 9564042.  
  • Gotoh Y, Cooper JA (1998). "Reactive oxygen species- and dimerization-induced activation of apoptosis signal-regulating kinase 1 in tumor necrosis factor-alpha signal transduction.". J. Biol. Chem. 273 (28): 17477–82. PMID 9651337.  
  • Chang HY, Nishitoh H, Yang X, et al. (1998). "Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx.". Science 281 (5384): 1860–3. PMID 9743501.  
  • Nishitoh H, Saitoh M, Mochida Y, et al. (1998). "ASK1 is essential for JNK/SAPK activation by TRAF2.". Mol. Cell 2 (3): 389–95. PMID 9774977.  
  • Wang XS, Diener K, Tan TH, Yao Z (1999). "MAPKKK6, a novel mitogen-activated protein kinase kinase kinase, that associates with MAPKKK5.". Biochem. Biophys. Res. Commun. 253 (1): 33–7. doi:10.1006/bbrc.1998.9749. PMID 9875215.  
  • Zhang L, Chen J, Fu H (1999). "Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins.". Proc. Natl. Acad. Sci. U.S.A. 96 (15): 8511–5. PMID 10411906.  
  • Hoeflich KP, Yeh WC, Yao Z, et al. (1999). "Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1).". Oncogene 18 (42): 5814–20. doi:10.1038/sj.onc.1202975. PMID 10523862.  
  • Takeda K, Hatai T, Hamazaki TS, et al. (2000). "Apoptosis signal-regulating kinase 1 (ASK1) induces neuronal differentiation and survival of PC12 cells.". J. Biol. Chem. 275 (13): 9805–13. PMID 10734135.  
  • Mochida Y, Takeda K, Saitoh M, et al. (2000). "ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction.". J. Biol. Chem. 275 (42): 32747–52. doi:10.1074/jbc.M003042200. PMID 10921914.  
  • Charette SJ, Lavoie JN, Lambert H, Landry J (2000). "Inhibition of Daxx-mediated apoptosis by heat shock protein 27.". Mol. Cell. Biol. 20 (20): 7602–12. PMID 11003656.  
  • McDonald PH, Chow CW, Miller WE, et al. (2000). "Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3.". Science 290 (5496): 1574–7. PMID 11090355.  
  • Ko YG, Kim EY, Kim T, et al. (2001). "Glutamine-dependent antiapoptotic interaction of human glutaminyl-tRNA synthetase with apoptosis signal-regulating kinase 1.". J. Biol. Chem. 276 (8): 6030–6. doi:10.1074/jbc.M006189200. PMID 11096076.  
  • Kim AH, Khursigara G, Sun X, et al. (2001). "Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1.". Mol. Cell. Biol. 21 (3): 893–901. doi:10.1128/MCB.21.3.893-901.2001. PMID 11154276.  
  • Cho SG, Lee YH, Park HS, et al. (2001). "Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1.". J. Biol. Chem. 276 (16): 12749–55. doi:10.1074/jbc.M005561200. PMID 11278289.  
  • Geleziunas R, Xu W, Takeda K, et al. (2001). "HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell.". Nature 410 (6830): 834–8. doi:10.1038/35071111. PMID 11298454.  
  • Xu XN, Screaton G (2001). "HIV-1 Nef: negative effector of Fas?". Nat. Immunol. 2 (5): 384–5. doi:10.1038/87682. PMID 11323689.  
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