The printable version is no longer supported and may have rendering errors. Please update your browser bookmarks and please use the default browser print function instead.
Dual specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4gene.[1]
This gene encodes a dual specificity protein kinase that belongs to the Ser/Thr protein kinase family. This kinase is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. It has been shown to activate MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38, but not MAPK1/ERK2 or MAPK3/ERK1. This kinase is phosphorylated, and thus activated by MAP3K1/MEKK. The knockout studies in mice suggested the roles of this kinase in mediating survival signal in T cell development, as well as in the organogenesis of liver.[2]
↑Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, Johnson GL, Karin M (May 1995). "Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2". Science. 268 (5208): 286–90. Bibcode:1995Sci...268..286L. doi:10.1126/science.7716521. PMID7716521.
↑Marti, A; Luo Z; Cunningham C; Ohta Y; Hartwig J; Stossel T P; Kyriakis J M; Avruch J (January 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. UNITED STATES. 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. ISSN0021-9258. PMID9006895.
↑ 5.05.1Park, Hee-Sae; Kim Mi-Sung; Huh Sung-Ho; Park Jihyun; Chung Jongkyeong; Kang Sang Sun; Choi Eui-Ju (January 2002). "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". J. Biol. Chem. United States. 277 (4): 2573–8. doi:10.1074/jbc.M110299200. ISSN0021-9258. PMID11707464.
↑Chen, Z; Cobb M H (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. United States. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. ISSN0021-9258. PMID11279118.
↑Matsuura, Hiroshi; Nishitoh Hideki; Takeda Kohsuke; Matsuzawa Atsushi; Amagasa Teruo; Ito Michihiko; Yoshioka Katsuji; Ichijo Hidenori (October 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. ISSN0021-9258. PMID12189133.
Yan M, Dai T, Deak JC, et al. (1995). "Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1". Nature. 372 (6508): 798–800. Bibcode:1994Natur.372..798Y. doi:10.1038/372798a0. PMID7997270.
Gale NW, Holland SJ, Valenzuela DM, et al. (1996). "Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis". Neuron. 17 (1): 9–19. doi:10.1016/S0896-6273(00)80276-7. PMID8755474.
White RA, Hughes RT, Adkison LR, et al. (1996). "The gene encoding protein kinase SEK1 maps to mouse chromosome 11 and human chromosome 17". Genomics. 34 (3): 430–2. doi:10.1006/geno.1996.0309. PMID8786147.
Nishina H, Fischer KD, Radvanyi L, et al. (1997). "Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3". Nature. 385 (6614): 350–3. Bibcode:1997Natur.385..350N. doi:10.1038/385350a0. PMID9002521.
Marti A, Luo Z, Cunningham C, et al. (1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. PMID9006895.
Deacon K, Blank JL (1997). "Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo". J. Biol. Chem. 272 (22): 14489–96. doi:10.1074/jbc.272.22.14489. PMID9162092.
Hirai S, Katoh M, Terada M, et al. (1997). "MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase". J. Biol. Chem. 272 (24): 15167–73. doi:10.1074/jbc.272.24.15167. PMID9182538.
Teng DH, Perry WL, Hogan JK, et al. (1997). "Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor". Cancer Res. 57 (19): 4177–82. PMID9331070.
Xu S, Cobb MH (1998). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". J. Biol. Chem. 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. PMID9405400.
Guan Z, Buckman SY, Pentland AP, et al. (1998). "Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway". J. Biol. Chem. 273 (21): 12901–8. doi:10.1074/jbc.273.21.12901. PMID9582321.
Su GH, Hilgers W, Shekher MC, et al. (1998). "Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene". Cancer Res. 58 (11): 2339–42. PMID9622070.
Yang J, New L, Jiang Y, et al. (1998). "Molecular cloning and characterization of a human protein kinase that specifically activates c-Jun N-terminal kinase". Gene. 212 (1): 95–102. doi:10.1016/S0378-1119(98)00158-9. PMID9661668.
Widegren U, Jiang XJ, Krook A, et al. (1998). "Divergent effects of exercise on metabolic and mitogenic signaling pathways in human skeletal muscle". FASEB J. 12 (13): 1379–89. PMID9761781.
Merritt SE, Mata M, Nihalani D, et al. (1999). "The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate". J. Biol. Chem. 274 (15): 10195–202. doi:10.1074/jbc.274.15.10195. PMID10187804.
Orth K, Palmer LE, Bao ZQ, et al. (1999). "Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector". Science. 285 (5435): 1920–3. doi:10.1126/science.285.5435.1920. PMID10489373.