MAPK1

Mitogen-activated protein kinase 1 (MAPK 1), also known as ERK2, is an enzyme that in humans is encoded by the MAPK1 gene.[5]

MAPK1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMAPK1, ERK, ERK-2, ERK2, ERT1, MAPK2, P42MAPK, PRKM1, PRKM2, p38, p40, p41, p41mapk, p42-MAPK, mitogen-activated protein kinase 1, NS13
External IDsOMIM: 176948 MGI: 1346858 HomoloGene: 37670 GeneCards: MAPK1
Orthologs
SpeciesHumanMouse
Entrez

5594

26413

Ensembl

ENSG00000100030

ENSMUSG00000063358

UniProt

P28482

P63085

RefSeq (mRNA)

NM_138957
NM_002745

NM_001038663
NM_011949
NM_001357115
NM_028991

RefSeq (protein)

NP_002736
NP_620407

NP_001033752
NP_036079
NP_001344044

Location (UCSC)Chr 22: 21.76 – 21.87 MbChr 16: 16.8 – 16.87 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), 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. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene.[6] MAPK1 contains multiple amino acid sites that are phosphorylated and ubiquitinated.[7]

Model organisms

Model organisms have been used in the study of MAPK1 function. A conditional knockout mouse line, called Mapk1tm1a(EUCOMM)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty seven tests were carried out on mutant mice and three significant abnormalities were observed.[12] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and males had decreased circulating amylase levels.[12]

Conditional deletion of Mapk1 in B cells showed a role for MAPK1 in T-cell-dependent antibody production.[20] A dominant gain-of-function mutant of Mapk1 in transgenic mice showed a role for MAPK1 in T-cell development.[21] Conditional inactivation of Mapk1 in neural progenitor cells of the developing cortex lead to a reduction of cortical thickness and reduced proliferation in neural progenitor cells.[22]

Interactions

MAPK1 has been shown to interact with:

Clinical significance

Mutations in MAPK1 are implicated in many types of cancer.[61]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000100030 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000063358 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  6. "Entrez Gene: MAPK1 mitogen-activated protein kinase 1".
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Further reading
  • Morishima-Kawashima M, Hasegawa M, Takio K, Suzuki M, Yoshida H, Watanabe A, Titani K, Ihara Y (1995). "Hyperphosphorylation of tau in PHF". Neurobiol. Aging. 16 (3): 365–71, discussion 371–80. doi:10.1016/0197-4580(95)00027-C. PMID 7566346. S2CID 22471158.
  • Jeong Y, Du R, Zhu X, et al. (2014). "Histone deacetylase isoforms regulate innate immune responses by deacetylating mitogen-activated protein kinase phosphatase-1". J Leukoc Biol. 95 (4): 651–9. doi:10.1189/jlb.1013565. PMID 24374966. S2CID 40126163.
  • Davis RJ (1995). "Transcriptional regulation by MAP kinases". Mol. Reprod. Dev. 42 (4): 459–67. doi:10.1002/mrd.1080420414. PMID 8607977. S2CID 12842112.
  • Peruzzi F, Gordon J, Darbinian N, Amini S (2002). "Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway". J. Neurovirol. 8 Suppl 2 (2): 91–6. doi:10.1080/13550280290167885. PMID 12491158.
  • Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (2003). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". J. Biosci. 28 (3): 323–35. doi:10.1007/BF02970151. PMID 12734410. S2CID 33749514.
  • Meloche S, Pouysségur J (2007). "The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition". Oncogene. 26 (22): 3227–39. doi:10.1038/sj.onc.1210414. PMID 17496918.
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