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MAPK7

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Main article: Mitogen-activated protein kinase
MAPK7
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMAPK7, BMK1, ERK4, ERK5, PRKM7, mitogen-activated protein kinase 7
External IDsOMIM: 602521; MGI: 1346347; HomoloGene: 2060; GeneCards: MAPK7; OMA:MAPK7 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5598

23939

Ensembl

ENSG00000166484

ENSMUSG00000001034

UniProt

Q13164

Q9WVS8

RefSeq (mRNA)

NM_002749
NM_139032
NM_139033
NM_139034

RefSeq (protein)

NP_002740
NP_620601
NP_620602
NP_620603

Location (UCSC)Chr 17: 19.38 – 19.38 MbChr 11: 61.49 – 61.49 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mitogen-activated protein kinase 7 also known as MAP kinase 7 is an enzyme that in humans is encoded by the MAPK7 gene.[5][6]

Function

MAPK7 is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor tyrosine kinases, and G protein-coupled receptors. In response to extracellular signals, this kinase translocates to the cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported.[7]

MAPK7 is also critical for cardiovascular development [8] and is essential for endothelial cell function.[9][10]

Interactions

MAPK7 has been shown to interact with:

ERK5 (= MAPK7) Inhibitors

XMD8-92 was one of the first described ERK5 inhibitors and was used in several pharmacological studies as tool compound. However, XMD8-92 hits BRD4 as an off-target[17] leading to false or inconclusive results. Consequently, ERK5 inhibitors with improved selectivity (void of the BRD4 off-target effect) such as AX15836[17] and BAY-885[18] were developed and should preferably be used for future pharmacological studies. BAY-885 fulfils the quality criteria for a 'Donated Chemical Probe' as defined by the Structural Genomics Consortium.[19] In 2020, it was demonstrated that ATP-competitive inhibitors paradoxically activate ERK5 signalling.[20] A recent review discussed the modulation of ERK5 activity as a therapeutic anti-cancer strategy.[21]

ERK5 (= MAPK7) Degrader

Based on a close analog of the ERK5 inhibitor BAY-885[18] the Proteolysis Targeting Chimera[22] (PROTAC) INY-06-061[23] was developed which allows to compare the phenotypes resulting from ERK5 inhibition versus degradation.

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000166484 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001034 – 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. ^ Purandare SM, Lee JD, Patel PI (March 1999). "Assignment of big MAP kinase (PRKM7) to human chromosome 17 band p11.2 with somatic cell hybrids". Cytogenetics and Cell Genetics. 83 (3–4): 258–259. doi:10.1159/000015199. PMID 10072598. S2CID 31186896.
  6. ^ a b Zhou G, Bao ZQ, Dixon JE (May 1995). "Components of a new human protein kinase signal transduction pathway". The Journal of Biological Chemistry. 270 (21): 12665–12669. doi:10.1074/jbc.270.21.12665. PMID 7759517.
  7. ^ "Entrez Gene: MAPK7 mitogen-activated protein kinase 7".
  8. ^ Hayashi M, Lee JD (December 2004). "Role of the BMK1/ERK5 signaling pathway: lessons from knockout mice". Journal of Molecular Medicine. 82 (12): 800–808. doi:10.1007/s00109-004-0602-8. PMID 15517128. S2CID 8499230.
  9. ^ Roberts OL, Holmes K, Müller J, Cross DA, Cross MJ (December 2009). "ERK5 and the regulation of endothelial cell function". Biochemical Society Transactions. 37 (Pt 6): 1254–1259. doi:10.1042/BST0371254. PMID 19909257.
  10. ^ Roberts OL, Holmes K, Müller J, Cross DA, Cross MJ (September 2010). "ERK5 is required for VEGF-mediated survival and tubular morphogenesis of primary human microvascular endothelial cells". Journal of Cell Science. 123 (Pt 18): 3189–3200. doi:10.1242/jcs.072801. PMID 20736307.
  11. ^ English JM, Pearson G, Hockenberry T, Shivakumar L, White MA, Cobb MH (October 1999). "Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control". The Journal of Biological Chemistry. 274 (44): 31588–31592. doi:10.1074/jbc.274.44.31588. PMID 10531364.
  12. ^ Cameron SJ, Malik S, Akaike M, Lerner-Marmarosh N, Yan C, Lee JD, et al. (May 2003). "Regulation of epidermal growth factor-induced connexin 43 gap junction communication by big mitogen-activated protein kinase1/ERK5 but not ERK1/2 kinase activation". The Journal of Biological Chemistry. 278 (20): 18682–18688. doi:10.1074/jbc.M213283200. PMID 12637502.
  13. ^ a b Yang CC, Ornatsky OI, McDermott JC, Cruz TF, Prody CA (October 1998). "Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Research. 26 (20): 4771–4777. doi:10.1093/nar/26.20.4771. PMC 147902. PMID 9753748.
  14. ^ Buschbeck M, Eickhoff J, Sommer MN, Ullrich A (August 2002). "Phosphotyrosine-specific phosphatase PTP-SL regulates the ERK5 signaling pathway". The Journal of Biological Chemistry. 277 (33): 29503–29509. doi:10.1074/jbc.M202149200. PMID 12042304.
  15. ^ Hayashi M, Tapping RI, Chao TH, Lo JF, King CC, Yang Y, Lee JD (March 2001). "BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase". The Journal of Biological Chemistry. 276 (12): 8631–8634. doi:10.1074/jbc.C000838200. PMID 11254654.
  16. ^ Zheng Q, Yin G, Yan C, Cavet M, Berk BC (March 2004). "14-3-3beta binds to big mitogen-activated protein kinase 1 (BMK1/ERK5) and regulates BMK1 function". The Journal of Biological Chemistry. 279 (10): 8787–8791. doi:10.1074/jbc.M310212200. PMID 14679215.
  17. ^ a b Lin EC, Amantea CM, Nomanbhoy TK, Weissig H, Ishiyama J, Hu Y, et al. (October 2016). "ERK5 kinase activity is dispensable for cellular immune response and proliferation". Proceedings of the National Academy of Sciences of the United States of America. 113 (42): 11865–11870. Bibcode:2016PNAS..11311865L. doi:10.1073/pnas.1609019113. PMC 5081620. PMID 27679845.
  18. ^ a b Nguyen D, Lemos C, Wortmann L, Eis K, Holton SJ, Boemer U, et al. (January 2019). "Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2- d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5". Journal of Medicinal Chemistry. 62 (2): 928–940. doi:10.1021/acs.jmedchem.8b01606. PMID 30563338. S2CID 56478089.
  19. ^ "Donated chemical probes". SGC. 2018-06-12. Retrieved 2023-07-26.
  20. ^ "Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for…". Biochemical Society Transactions.
  21. ^ "Modulation of ERK5 Activity as a Therapeutic Anti-Cancer Strategy". Journal of Medicinal Chemistry.
  22. ^ Luh LM, Scheib U, Juenemann K, Wortmann L, Brands M, Cromm PM (September 2020). "Prey for the Proteasome: Targeted Protein Degradation-A Medicinal Chemist's Perspective". Angewandte Chemie. 59 (36): 15448–15466. doi:10.1002/anie.202004310. PMC 7496094. PMID 32428344.
  23. ^ You I, Donovan KA, Krupnick NM, Boghossian AS, Rees MG, Ronan MM, et al. (November 2022). "Acute pharmacological degradation of ERK5 does not inhibit cellular immune response or proliferation". Cell Chemical Biology. 29 (11): 1630–1638.e7. doi:10.1016/j.chembiol.2022.09.004. PMC 9675722. PMID 36220104.{{cite journal}}: CS1 maint: PMC embargo expired (link)

Further reading

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