Biology:MAP2K4

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Short description: Protein-coding gene in the species Homo sapiens
Main page: Biology:Mitogen-activated protein kinase kinase


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Dual-specificity mitogen-activated protein kinase kinase 4 is an enzyme that in humans is encoded by the MAP2K4 gene.[1]

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).[2] MAP2K4 contains multiple amino acid sites that are phosphorylated and ubiquitinated.[3] Genetic studies using Map2k4 knockout mice revealed embryonic lethality, impaired hepatogenesis and defective liver formation.[4][5] Analysis of chimeric mice identified a role for Map2k4 in T cell cytokine production and proliferation.[6] Map2k4-deficient chimeric mice frequently develop lymphadenopathy.[7] MAP2K4 is altered in 1.97% of all human cancers.[8]

Interactions

MAP2K4 has been shown to interact with:


References

  1. ↑ "Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2". Science 268 (5208): 286–90. April 1995. doi:10.1126/science.7716521. PMID 7716521. Bibcode: 1995Sci...268..286L. 
  2. ↑ "P45985 | SWISS-MODEL Repository". https://swissmodel.expasy.org/repository/uniprot/P45985. 
  3. ↑ "MKK4 (human)". https://www.phosphosite.org/proteinAction.action?id=659&showAllSites=true. 
  4. ↑ "Defective liver formation and liver cell apoptosis in mice lacking the stress signaling kinase SEK1/MKK4". Development 126 (3): 505–16. February 1999. doi:10.1242/dev.126.3.505. PMID 9876179. 
  5. ↑ "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. June 1998. doi:10.1073/pnas.95.12.6881. PMID 9618507. Bibcode: 1998PNAS...95.6881G. 
  6. ↑ "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. September 1997. doi:10.1084/jem.186.6.941. PMID 9294148. 
  7. ↑ "SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development". Immunity 8 (5): 625–34. May 1998. doi:10.1016/s1074-7613(00)80567-1. PMID 9620683. 
  8. ↑ "MAP2K4 - My Cancer Genome". https://www.mycancergenome.org/content/gene/map2k4/. 
  9. ↑ "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. November 1998. doi:10.1101/gad.12.21.3369. PMID 9808624. 
  10. ↑ "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. January 1997. doi:10.1074/jbc.272.5.2620. PMID 9006895. 
  11. ↑ "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. October 2002. doi:10.1073/pnas.232310199. PMID 12391307. Bibcode: 2002PNAS...9914189L. 
  12. ↑ 12.0 12.1 "Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation". The Journal of Biological Chemistry 277 (4): 2573–8. January 2002. doi:10.1074/jbc.M110299200. PMID 11707464. 
  13. ↑ "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". The Journal of Biological Chemistry 276 (19): 16070–5. May 2001. doi:10.1074/jbc.M100681200. PMID 11279118. 
  14. ↑ "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. July 1997. doi:10.1073/pnas.94.14.7337. PMID 9207092. Bibcode: 1997PNAS...94.7337T. 
  15. ↑ "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. April 2000. doi:10.1128/MCB.20.7.2334-2342.2000. PMID 10713157. 
  16. ↑ "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. November 1999. doi:10.1128/mcb.19.11.7539. PMID 10523642. 
  17. ↑ "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. October 2002. doi:10.1074/jbc.M202004200. PMID 12189133. 
  18. ↑ "MKK4/SEK1 is negatively regulated through a feedback loop involving the E3 ubiquitin ligase itch". The Journal of Biological Chemistry 284 (43): 29399–29404. October 2009. doi:10.1074/jbc.M109.044958. PMID 19737936. 

Further reading

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



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