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MAPK15

MAPK15
Identifiers
AliasesMAPK15, ERK7, ERK8, mitogen-activated protein kinase 15
External IDsMGI: 2652894; HomoloGene: 16371; GeneCards: MAPK15; OMA:MAPK15 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

225689

332110

Ensembl

ENSG00000181085
ENSG00000274205

ENSMUSG00000063704

UniProt

Q8TD08

Q80Y86

RefSeq (mRNA)

NM_139021

NM_177922

RefSeq (protein)

NP_620590

NP_808590

Location (UCSC)Chr 8: 143.72 – 143.72 MbChr 15: 75.87 – 75.87 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Mitogen-activated protein kinase 15, also known as MAPK15, ERK7, or ERK8, is an enzyme that in humans is encoded by the MAPK15 gene.[5][6]

Evolutionarily, MAPK15 is conserved in a number of species, including P. troglodytes, B. taurus, M. musculus, R. norvegicus, D. rerio, D. melanogaster, C. elegans, and X. laevis.[6]

Function

The protein encoded by this gene is a member of the MAP (mitogen-activated protein) kinase family. MAP kinases are also known as extracellular signal-regulated kinases (ERKs), and are involved in signaling cascades that regulate a number of cellular processes, including proliferation, differentiation, and transcriptional regulation. MAPK15 is often referred to as ERK7 or ERK8, and the latter two share 69% amino acid sequence similarity; at least one study has suggested that the two are, in fact, distinct proteins.

In vertebrate models, ERK8 is not constitutively active, and exhibits relatively low basal kinase activity.[7] It contains two SH3 (SRC homology 3) binding motifs in its C-terminal region, and is likely activated by an SRC-dependent signaling pathway.[5] SRC is a non-receptor tyrosine kinase (and proto-oncogene) that has been implicated in cancer growth and progression in humans when it is overexpressed. The exact function of MAPK15 is unknown, though a number of studies have implicated the enzyme in various cellular pathways.

Specifically, MAPK15 expression is significantly reduced in human lung and breast carcinomas, and MAPK15 down-regulation is correlated with increased cell motility.[7] MAPK15 has also been found to negatively regulate protein O-glycosylation with acetyl galactosamine (GalNAc), a process in which a sugar molecule is covalently attached to an oxygen atom on an amino acid residue.[7] Mammalian MAPK15 is a putative regulator of the cellular localization and transcriptional activity of estrogen-related receptor alpha (ERRa), as well as an inhibitor of proliferating cell nuclear antigen (PCNA) degradation.[8][9] PCNA is critical for DNA replication, and is an essential factor in protecting genome stability. MAPK15 has also been shown to regulate ciliogenesis in X. laevis (African clawed frog) embryos by phosphorylating an actin regulator called CapZIP.[10]

Interactions

MAPK15 has been demonstrated to interact with gamma-aminobutyric acid receptor-associated protein (GABARAP) and microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A, or LC3) in a process that stimulates autophagy.[11] A number of additional proteins also interact with MAPK15, including cyclin-dependent kinase 2 (CDK2), mitogen-activated protein kinase 12 (MAPK12), and lactotransferrin (LTF), among many others.[6]

Clinical significance

Due to its role in protecting genomic integrity and cell motility, MAPK15 has been identified as a potential target for cancer therapeutics.[12] Additionally, given the putative role that MAPK15 plays in the regulation of ciliogenesis, it may be an ideal target for diseases related to human ciliary defects (often called ciliopathies).

References

  1. ^ a b c ENSG00000274205 GRCh38: Ensembl release 89: ENSG00000181085, ENSG00000274205 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000063704 – 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. ^ a b Abe MK, Saelzler MP, Espinosa R, Kahle KT, Hershenson MB, Le Beau MM, Rosner MR (May 2002). "ERK8, a new member of the mitogen-activated protein kinase family". The Journal of Biological Chemistry. 277 (19): 16733–43. doi:10.1074/jbc.M112483200. PMID 11875070.
  6. ^ a b c "Entrez Gene: MAPK15 mitogen-activated protein kinase 15".
  7. ^ a b c Chia J, Tham KM, Gill DJ, Bard-Chapeau EA, Bard FA (2014). "ERK8 is a negative regulator of O-GalNAc glycosylation and cell migration". eLife. 3: e01828. doi:10.7554/eLife.01828. PMC 3945522. PMID 24618899.
  8. ^ Rossi M, Colecchia D, Iavarone C, Strambi A, Piccioni F, Verrotti di Pianella A, Chiariello M (Mar 2011). "Extracellular signal-regulated kinase 8 (ERK8) controls estrogen-related receptor α (ERRα) cellular localization and inhibits its transcriptional activity". The Journal of Biological Chemistry. 286 (10): 8507–22. doi:10.1074/jbc.M110.179523. PMC 3048734. PMID 21190936.
  9. ^ Groehler AL, Lannigan DA (Aug 2010). "A chromatin-bound kinase, ERK8, protects genomic integrity by inhibiting HDM2-mediated degradation of the DNA clamp PCNA". The Journal of Cell Biology. 190 (4): 575–86. doi:10.1083/jcb.201002124. PMC 2928013. PMID 20733054.
  10. ^ Miyatake K, Kusakabe M, Takahashi C, Nishida E (2015). "ERK7 regulates ciliogenesis by phosphorylating the actin regulator CapZIP in cooperation with Dishevelled". Nature Communications. 6: 6666. Bibcode:2015NatCo...6.6666M. doi:10.1038/ncomms7666. PMID 25823377.
  11. ^ Colecchia D, Strambi A, Sanzone S, Iavarone C, Rossi M, Dall'Armi C, Piccioni F, Verrotti di Pianella A, Chiariello M (Dec 2012). "MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins". Autophagy. 8 (12): 1724–40. doi:10.4161/auto.21857. PMC 3541284. PMID 22948227.
  12. ^ Strambi A, Mori M, Rossi M, Colecchia D, Manetti F, Carlomagno F, Botta M, Chiariello M (2013). "Structure prediction and validation of the ERK8 kinase domain". PLOS ONE. 8 (1): e52011. Bibcode:2013PLoSO...852011S. doi:10.1371/journal.pone.0052011. PMC 3543423. PMID 23326322.

Further reading

Quelle: http://en.wikipedia.org/wiki/MAPK15