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Wikipedia

MAP2K4

March 28, 2023

Main article: Mitogen-activated protein kinase kinase

Dual-specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene.[5]

MAP2K4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMAP2K4, JNKK, JNKK1, MAPKK4, MEK4, MKK4, PRKMK4, SAPKK-1, SAPKK1, SEK1, SERK1, SKK1, mitogen-activated protein kinase kinase 4
External IDsOMIM: 601335 MGI: 1346869 HomoloGene: 48159 GeneCards: MAP2K4
Orthologs
SpeciesHumanMouse
Entrez

6416

26398

Ensembl

ENSG00000065559

ENSMUSG00000033352

UniProt

P45985

P47809

RefSeq (mRNA)

NM_001281435
NM_003010

RefSeq (protein)

NP_001268364
NP_003001

Location (UCSC)Chr 17: 12.02 – 12.14 MbChr 11: 65.58 – 65.68 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

MAP2K4 encodes a dual-specificity kinase that belongs to the Ser/Thr protein kinase family. MAP2K4 phosphorylates MAP kinases in response to various environmental stresses or mitogenic stimuli. MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38 are substrates for MAP2K4, but MAPK1/ERK2 and MAPK3/ERK1 are not phosphorylated by MAP2K4. Structurally, MAP2K4 contains a kinase domain that is phosphorylated and activated by MAP3K1(aka MEKK1).[6] MAP2K4 contains multiple amino acid sites that are phosphorylated and ubiquitinated.[7] Genetic studies using Map2k4 knockout mice revealed embryonic lethality, impaired hepatogenesis and defective liver formation.[8][9] Analysis of chimeric mice identified a role for Map2k4 in T cell cytokine production and proliferation.[10] Map2k4-deficient chimeric mice frequently develop lymphadenopathy.[11] MAP2K4 is altered in 1.97% of all human cancers.[12]

Interactions

MAP2K4 has been shown to interact with:


References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000065559 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033352 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Lin A, Minden A, Martinetto H, Claret FX, Lange-Carter C, Mercurio F, et al. (April 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. PMID 7716521.
  6. ^ "P45985 | SWISS-MODEL Repository".
  7. ^ "MKK4 (human)". www.phosphosite.org. Retrieved 2020-10-28.
  8. ^ Nishina H, Vaz C, Billia P, Nghiem M, Sasaki T, De la Pompa JL, et al. (February 1999). "Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4". Development. 126 (3): 505–16. doi:10.1242/dev.126.3.505. PMID 9876179.
  9. ^ Ganiatsas S, Kwee L, Fujiwara Y, Perkins A, Ikeda T, Labow MA, Zon LI (June 1998). "SEK1 deficiency reveals mitogen-activated protein kinase cascade crossregulation and leads to abnormal hepatogenesis". Proceedings of the National Academy of Sciences of the United States of America. 95 (12): 6881–6. Bibcode:1998PNAS...95.6881G. doi:10.1073/pnas.95.12.6881. PMC 22670. PMID 9618507.
  10. ^ Nishina H, Bachmann M, Oliveira-dos-Santos AJ, Kozieradzki I, Fischer KD, Odermatt B, et al. (September 1997). "Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes". The Journal of Experimental Medicine. 186 (6): 941–53. doi:10.1084/jem.186.6.941. PMC 2199046. PMID 9294148.
  11. ^ Swat W, Fujikawa K, Ganiatsas S, Yang D, Xavier RJ, Harris NL, et al. (May 1998). "SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development". Immunity. 8 (5): 625–34. doi:10.1016/s1074-7613(00)80567-1. PMID 9620683.
  12. ^ "MAP2K4 - My Cancer Genome". www.mycancergenome.org. Retrieved 2020-12-26.
  13. ^ Xia Y, Wu Z, Su B, Murray B, Karin M (November 1998). "JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension". Genes & Development. 12 (21): 3369–81. doi:10.1101/gad.12.21.3369. PMC 317229. PMID 9808624.
  14. ^ Marti A, Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel TP, et al. (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". The Journal of Biological Chemistry. 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. PMID 9006895.
  15. ^ Lee CM, Onésime D, Reddy CD, Dhanasekaran N, Reddy EP (October 2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proceedings of the National Academy of Sciences of the United States of America. 99 (22): 14189–94. Bibcode:2002PNAS...9914189L. doi:10.1073/pnas.232310199. PMC 137859. PMID 12391307.
  16. ^ a b Park HS, Kim MS, Huh SH, Park J, Chung J, Kang SS, Choi EJ (January 2002). "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". The Journal of Biological Chemistry. 277 (4): 2573–8. doi:10.1074/jbc.M110299200. PMID 11707464.
  17. ^ Chen Z, Cobb MH (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". The Journal of Biological Chemistry. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.
  18. ^ Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proceedings of the National Academy of Sciences of the United States of America. 94 (14): 7337–42. Bibcode:1997PNAS...94.7337T. doi:10.1073/pnas.94.14.7337. PMC 23822. PMID 9207092.
  19. ^ Cheng J, Yang J, Xia Y, Karin M, Su B (April 2000). "Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation". Molecular and Cellular Biology. 20 (7): 2334–42. doi:10.1128/MCB.20.7.2334-2342.2000. PMC 85399. PMID 10713157.
  20. ^ Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, et al. (November 1999). "JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway". Molecular and Cellular Biology. 19 (11): 7539–48. doi:10.1128/mcb.19.11.7539. PMC 84763. PMID 10523642.
  21. ^ Matsuura H, Nishitoh H, Takeda K, Matsuzawa A, Amagasa T, Ito M, et al. (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". The Journal of Biological Chemistry. 277 (43): 40703–9. doi:10.1074/jbc.M202004200. PMID 12189133.
  22. ^ Ahn YH, Kurie JM (October 2009). "MKK4/SEK1 is negatively regulated through a feedback loop involving the E3 ubiquitin ligase itch". The Journal of Biological Chemistry. 284 (43): 29399–29404. doi:10.1074/jbc.M109.044958. PMC 2785572. PMID 19737936.

Further reading

  • Lin, A (2006). "The JNK Signaling Pathway (Molecular Biology Intelligence Unit)". Landes Bioscience. 1: 1–97. ISBN 978-1587061202.

March 28, 2023
map2k4, main, article, mitogen, activated, protein, kinase, kinase, dual, specificity, mitogen, activated, protein, kinase, kinase, enzyme, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes3aln, 3alo, 3vutidentifiersa. Main article Mitogen activated protein kinase kinase Dual specificity mitogen activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene 5 MAP2K4Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes3ALN 3ALO 3VUTIdentifiersAliasesMAP2K4 JNKK JNKK1 MAPKK4 MEK4 MKK4 PRKMK4 SAPKK 1 SAPKK1 SEK1 SERK1 SKK1 mitogen activated protein kinase kinase 4External IDsOMIM 601335 MGI 1346869 HomoloGene 48159 GeneCards MAP2K4Gene location Human Chr Chromosome 17 human 1 Band17p12Start12 020 829 bp 1 End12 143 830 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 B3 11 40 53 cMStart65 579 069 bp 2 End65 679 123 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inBrodmann area 46postcentral gyrusorbitofrontal cortexmiddle temporal gyrussuperior frontal gyrusprefrontal cortexAchilles tendonBrodmann area 23ponsBrodmann area 9Top expressed infacial motor nucleussuperior frontal gyrusanterior horn of spinal cordsecondary oocytedorsomedial hypothalamic nucleusparaventricular nucleus of hypothalamusventral tegmental areamedial dorsal nucleussubiculumhippocampus properMore reference expression dataBioGPSn aGene ontologyMolecular functiontransferase activity protein kinase activity nucleotide binding kinase activity protein binding protein tyrosine kinase activity ATP binding MAP kinase kinase activity JUN kinase kinase activity protein serine threonine kinase activity mitogen activated protein kinase kinase kinase bindingCellular componentcytoplasm nucleus dendrite cytoplasm cytosol perikaryon axonBiological processphosphorylation MAPK cascade protein phosphorylation cellular response to mechanical stimulus response to wounding peptidyl tyrosine phosphorylation signal transduction negative regulation of motor neuron apoptotic process apoptotic process cell growth involved in cardiac muscle cell development cellular response to sorbitol positive regulation of smooth muscle cell apoptotic process JNK cascade positive regulation of protein phosphorylation positive regulation of neuron apoptotic process positive regulation of DNA replication positive regulation of apoptotic process positive regulation of nitric oxide synthase biosynthetic process regulation of mitotic cell cycle stress activated protein kinase signaling cascade activation of protein kinase activity regulation of apoptotic process Fc epsilon receptor signaling pathwaySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez641626398EnsemblENSG00000065559ENSMUSG00000033352UniProtP45985P47809RefSeq mRNA NM 001281435NM 003010NM 009157NM 001316367NM 001316368NM 001316369NM 001362739NM 001362740RefSeq protein NP 001268364NP 003001NP 001303296NP 001303297NP 001303298NP 033183NP 001349668NP 001349669Location UCSC Chr 17 12 02 12 14 MbChr 11 65 58 65 68 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseMAP2K4 encodes a dual specificity kinase that belongs to the Ser Thr protein kinase family MAP2K4 phosphorylates MAP kinases in response to various environmental stresses or mitogenic stimuli MAPK8 JNK1 MAPK9 JNK2 and MAPK14 p38 are substrates for MAP2K4 but MAPK1 ERK2 and MAPK3 ERK1 are not phosphorylated by MAP2K4 Structurally MAP2K4 contains a kinase domain that is phosphorylated and activated by MAP3K1 aka MEKK1 6 MAP2K4 contains multiple amino acid sites that are phosphorylated and ubiquitinated 7 Genetic studies using Map2k4 knockout mice revealed embryonic lethality impaired hepatogenesis and defective liver formation 8 9 Analysis of chimeric mice identified a role for Map2k4 in T cell cytokine production and proliferation 10 Map2k4 deficient chimeric mice frequently develop lymphadenopathy 11 MAP2K4 is altered in 1 97 of all human cancers 12 Interactions EditMAP2K4 has been shown to interact with MAP3K1 13 FLNC 14 MAPK8 15 16 17 18 19 MAPK8IP3 20 21 and AKT1 16 ITCH 22 References Edit a b c GRCh38 Ensembl release 89 ENSG00000065559 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000033352 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Lin A Minden A Martinetto H Claret FX Lange Carter C Mercurio F et al April 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 PMID 7716521 P45985 SWISS MODEL Repository MKK4 human www phosphosite org Retrieved 2020 10 28 Nishina H Vaz C Billia P Nghiem M Sasaki T De la Pompa JL et al February 1999 Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1 MKK4 Development 126 3 505 16 doi 10 1242 dev 126 3 505 PMID 9876179 Ganiatsas S Kwee L Fujiwara Y Perkins A Ikeda T Labow MA Zon LI June 1998 SEK1 deficiency reveals mitogen activated protein kinase cascade crossregulation and leads to abnormal hepatogenesis Proceedings of the National Academy of Sciences of the United States of America 95 12 6881 6 Bibcode 1998PNAS 95 6881G doi 10 1073 pnas 95 12 6881 PMC 22670 PMID 9618507 Nishina H Bachmann M Oliveira dos Santos AJ Kozieradzki I Fischer KD Odermatt B et al September 1997 Impaired CD28 mediated interleukin 2 production and proliferation in stress kinase SAPK ERK1 kinase SEK1 mitogen activated protein kinase kinase 4 MKK4 deficient T lymphocytes The Journal of Experimental Medicine 186 6 941 53 doi 10 1084 jem 186 6 941 PMC 2199046 PMID 9294148 Swat W Fujikawa K Ganiatsas S Yang D Xavier RJ Harris NL et al May 1998 SEK1 MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development Immunity 8 5 625 34 doi 10 1016 s1074 7613 00 80567 1 PMID 9620683 MAP2K4 My Cancer Genome www mycancergenome org Retrieved 2020 12 26 Xia Y Wu Z Su B Murray B Karin M November 1998 JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino terminal extension Genes amp Development 12 21 3369 81 doi 10 1101 gad 12 21 3369 PMC 317229 PMID 9808624 Marti A Luo Z Cunningham C Ohta Y Hartwig J Stossel TP et al 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 The Journal of Biological Chemistry 272 5 2620 8 doi 10 1074 jbc 272 5 2620 PMID 9006895 Lee CM Onesime D Reddy CD Dhanasekaran N Reddy EP October 2002 JLP A scaffolding protein that tethers JNK p38MAPK signaling modules and transcription factors Proceedings of the National Academy of Sciences of the United States of America 99 22 14189 94 Bibcode 2002PNAS 9914189L doi 10 1073 pnas 232310199 PMC 137859 PMID 12391307 a b Park HS Kim MS Huh SH Park J Chung J Kang SS Choi EJ January 2002 Akt protein kinase B negatively regulates SEK1 by means of protein phosphorylation The Journal of Biological Chemistry 277 4 2573 8 doi 10 1074 jbc M110299200 PMID 11707464 Chen Z Cobb MH May 2001 Regulation of stress responsive mitogen activated protein MAP kinase pathways by TAO2 The Journal of Biological Chemistry 276 19 16070 5 doi 10 1074 jbc M100681200 PMID 11279118 Tournier C Whitmarsh AJ Cavanagh J Barrett T Davis RJ July 1997 Mitogen activated protein kinase kinase 7 is an activator of the c Jun NH2 terminal kinase Proceedings of the National Academy of Sciences of the United States of America 94 14 7337 42 Bibcode 1997PNAS 94 7337T doi 10 1073 pnas 94 14 7337 PMC 23822 PMID 9207092 Cheng J Yang J Xia Y Karin M Su B April 2000 Synergistic interaction of MEK kinase 2 c Jun N terminal kinase JNK kinase 2 and JNK1 results in efficient and specific JNK1 activation Molecular and Cellular Biology 20 7 2334 42 doi 10 1128 MCB 20 7 2334 2342 2000 PMC 85399 PMID 10713157 Ito M Yoshioka K Akechi M Yamashita S Takamatsu N Sugiyama K et al November 1999 JSAP1 a novel jun N terminal protein kinase JNK binding protein that functions as a Scaffold factor in the JNK signaling pathway Molecular and Cellular Biology 19 11 7539 48 doi 10 1128 mcb 19 11 7539 PMC 84763 PMID 10523642 Matsuura H Nishitoh H Takeda K Matsuzawa A Amagasa T Ito M et al 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 The Journal of Biological Chemistry 277 43 40703 9 doi 10 1074 jbc M202004200 PMID 12189133 Ahn YH Kurie JM October 2009 MKK4 SEK1 is negatively regulated through a feedback loop involving the E3 ubiquitin ligase itch The Journal of Biological Chemistry 284 43 29399 29404 doi 10 1074 jbc M109 044958 PMC 2785572 PMID 19737936 Further reading EditLin A 2006 The JNK Signaling Pathway Molecular Biology Intelligence Unit Landes Bioscience 1 1 97 ISBN 978 1587061202 Portal Biology Retrieved from https en wikipedia org w index php title MAP2K4 amp oldid 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