MAPK3 explained

See main article: Extracellular signal-regulated kinases.

Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1,^[1] is an enzyme that in humans is encoded by the MAPK3 gene.^[2]

Function

The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described.^[3]

Clinical significance

It has been suggested that MAPK3, along with the gene IRAK1, is turned off by two microRNAs that were activated after the influenza A virus had been made to infect human lung cells.^[4]

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK3β activity and protein synthesis levels in a model of tuberous sclerosis.^[5]

Interactions

MAPK3 has been shown to interact with:

• DUSP3,^[6]
• DUSP6^[7]
• GTF2I,^[8]
• HDAC4,^[9]
• MAP2K1,^{[10] [11] [12] [13]}
• MAP2K2,^{[10] [11] [13]}
• PTPN7,^{[14] [15] [16]}
• RPS6KA2,^{[17] [18]} and
• SPIB.^[19]

Further reading

• Peruzzi F, Gordon J, Darbinian N, Amini S . Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway . J. Neurovirol. . 8 Suppl 2 . 2 . 91–6 . 2002 . 12491158 . 10.1080/13550280290167885 .
• Meloche S, Pouysségur J . The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition . Oncogene . 26 . 22 . 3227–39 . 2007 . 17496918 . 10.1038/sj.onc.1210414 . free .

External links

• MAP Kinase Resource .

Notes and References

1. Thomas. Gareth M.. Huganir. Richard L.. 1 March 2004. MAPK cascade signalling and synaptic plasticity. Nature Reviews Neuroscience. 5. 3. 173–183. 10.1038/nrn1346. 14976517. 205499891. 1471-003X.
2. García F, Zalba G, Páez G, Encío I, de Miguel C . Molecular cloning and characterization of the human p44 mitogen-activated protein kinase gene . Genomics . 50 . 1 . 69–78 . 15 May 1998 . 9628824 . 10.1006/geno.1998.5315 .
3. Web site: Entrez Gene: MAPK3 mitogen-activated protein kinase 3.
4. Buggele WA, Johnson KE, Horvath CM . Influenza A virus infection of human respiratory cells induces primary microRNA expression . J. Biol. Chem. . 287 . 37 . 31027–40 . 2012 . 22822053 . 3438935 . 10.1074/jbc.M112.387670 . free .
5. Pal R, Bondar VV, Adamski CJ, Rodney GG, Sardiello M . Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis . Sci. Rep. . 7 . 1 . 4174 . 2017 . 28646232 . 10.1038/s41598-017-04528-5 . 5482840. 2017NatSR...7.4174P .
6. Todd JL, Tanner KG, Denu JM . Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway . J. Biol. Chem. . 274 . 19 . 13271–80 . May 1999 . 10224087 . 10.1074/jbc.274.19.13271. free .
7. Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, Boschert U, Rodrigues N, Davies K, Ashworth A, Arkinstall S . The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity . J. Biol. Chem. . 273 . 15 . 9323–9 . April 1998 . 9535927 . 10.1074/jbc.273.15.9323. free .
8. Kim DW, Cochran BH . Extracellular signal-regulated kinase binds to TFII-I and regulates its activation of the c-fos promoter . Mol. Cell. Biol. . 20 . 4 . 1140–8 . February 2000 . 10648599 . 85232 . 10.1128/mcb.20.4.1140-1148.2000.
9. Zhou X, Richon VM, Wang AH, Yang XJ, Rifkind RA, Marks PA . Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras . Proc. Natl. Acad. Sci. U.S.A. . 97 . 26 . 14329–33 . December 2000 . 11114188 . 18918 . 10.1073/pnas.250494697 . 2000PNAS...9714329Z . free .
10. Marti A, Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel TP, Kyriakis JM, Avruch J . 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 . J. Biol. Chem. . 272 . 5 . 2620–8 . January 1997 . 9006895 . 10.1074/jbc.272.5.2620. free .
11. Butch ER, Guan KL . Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2 . J. Biol. Chem. . 271 . 8 . 4230–5 . February 1996 . 8626767 . 10.1074/jbc.271.8.4230. free .
12. Elion EA . Routing MAP kinase cascades . Science . 281 . 5383 . 1625–6 . September 1998 . 9767029 . 10.1126/science.281.5383.1625. 28868990 .
13. Zheng CF, Guan KL . Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases . J. Biol. Chem. . 268 . 32 . 23933–9 . November 1993 . 10.1016/S0021-9258(20)80474-8 . 8226933 . free .
14. Pettiford SM, Herbst R . The MAP-kinase ERK2 is a specific substrate of the protein tyrosine phosphatase HePTP . Oncogene . 19 . 7 . 858–69 . February 2000 . 10702794 . 10.1038/sj.onc.1203408 . free .
15. Saxena M, Williams S, Taskén K, Mustelin T . Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase . Nat. Cell Biol. . 1 . 5 . 305–11 . September 1999 . 10559944 . 10.1038/13024 . 40413956 .
16. Saxena M, Williams S, Brockdorff J, Gilman J, Mustelin T . Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP) . J. Biol. Chem. . 274 . 17 . 11693–700 . April 1999 . 10206983 . 10.1074/jbc.274.17.11693. free .
17. Roux PP, Richards SA, Blenis J . Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity . Mol. Cell. Biol. . 23 . 14 . 4796–804 . July 2003 . 12832467 . 162206 . 10.1128/mcb.23.14.4796-4804.2003.
18. Zhao Y, Bjorbaek C, Moller DE . Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases . J. Biol. Chem. . 271 . 47 . 29773–9 . November 1996 . 8939914 . 10.1074/jbc.271.47.29773. free .
19. Mao C, Ray-Gallet D, Tavitian A, Moreau-Gachelin F . Differential phosphorylations of Spi-B and Spi-1 transcription factors . Oncogene . 12 . 4 . 863–73 . February 1996 . 8632909 .