Extracellular signal-regulated kinases
Template:Short description Script error: No such module "Labelled list hatnote". In molecular biology, extracellular signal-regulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells. Many different stimuli, including growth factors, cytokines, virus infection, ligands for heterotrimeric G protein-coupled receptors, transforming agents, and carcinogens, activate the ERK pathway.[citation needed]
The term, "extracellular signal-regulated kinases", is sometimes used as a synonym for mitogen-activated protein kinase (MAPK), but has more recently been adopted for a specific subset of the mammalian MAPK family.[citation needed]
In the MAPK/ERK pathway, Ras activates c-Raf, which in turn phosphorylates a mitogen-activated protein kinase kinase (abbreviated as MKK, MEK, or MAP2K), which subsequently phosphorylates one or more ERKs, such as MAPK1/2 (below). Ras is typically activated by growth hormones through receptor tyrosine kinases and GRB2/SOS, but may also be activated by other signals. ERKs can activate many transcription factors, such as ELK1,[1] and other downstream protein kinases.
Disruption of the ERK pathway commonly leads to cancers, especially when caused by mutations in Ras, c-Raf, or receptors such as HER2.
Mitogen-activated protein kinase 1
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| mitogen-activated protein kinase 1 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | MAPK1 | ||||||
| Alt. symbols | PRKM2, PRKM1 | ||||||
| NCBI gene | 5594 | ||||||
| HGNC | 6871 | ||||||
| OMIM | 176948 | ||||||
| RefSeq | NM_002745 | ||||||
| UniProt | P28482 | ||||||
| Other data | |||||||
| Locus | Chr. 22 q11.2 | ||||||
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Mitogen-activated protein kinase 1 (MAPK1) is also known as extracellular signal-regulated kinase 2 (ERK2). Two similar protein kinases with 85% sequence identity were originally called ERK1 and ERK2.[2] They were found during a search for protein kinases that are rapidly phosphorylated after activation of cell surface tyrosine kinases such as the epidermal growth factor receptor. Phosphorylation of ERKs leads to the activation of their kinase activity.
The molecular events linking cell surface receptors to activation of ERKs are complex. It was found that Ras GTP-binding proteins are involved in the activation of ERKs.[3] Another protein kinase, Raf-1, was shown to phosphorylate a "MAP kinase-kinase", thus qualifying as a "MAP kinase kinase kinase".[4] The MAP kinase-kinase, which activates ERK, was named "MAPK/ERK kinase" (MEK).[5]
Receptor-linked tyrosine kinases, Ras, Raf, MEK, and MAPK could be fitted into a signaling cascade linking an extracellular signal to MAPK activation.[6] See: MAPK/ERK pathway.
Transgenic gene knockout mice lacking MAPK1 have major defects in early development.[7] Conditional deletion of Mapk1 in B cells showed a role for MAPK1 in T-cell-dependent antibody production.[8] A dominant gain-of-function mutant of Mapk1 in transgenic mice showed a role for MAPK1 in T-cell development.[9] 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.[10]
Mitogen-activated protein kinase 3
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| mitogen-activated protein kinase 3 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | MAPK3 | ||||||
| Alt. symbols | PRKM3 | ||||||
| NCBI gene | 5595 | ||||||
| HGNC | 6877 | ||||||
| OMIM | 601795 | ||||||
| RefSeq | NM_001040056 | ||||||
| UniProt | P27361 | ||||||
| Other data | |||||||
| Locus | Chr. 16 p11.2 | ||||||
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Mitogen-activated protein kinase 3 (MAPK3) is also known as extracellular signal-regulated kinase 1 (ERK1). Transgenic gene knockout mice lacking MAPK3 are viable and it is thought that MAPK1 can fulfill some MAPK3 functions in most cells.[11] The main exception is in T cells. Mice lacking MAPK3 have reduced T cell development past the CD4+ and CD8+ stage.
Mitogen-activated protein kinase 7
Mitogen-activated protein kinase 7 (MAPK7) is also known as extracellular signal-regulated kinase 5 (ERK5). Sometimes referred to as Big MAPK or BMK due to its large size in comparison to other MAPKs.[12]
Clinical significance
Activation of the ERK1/2 pathway by aberrant RAS/RAF signalling, DNA damage, and oxidative stress leads to cellular senescence.[13] Low doses of DNA damage resulting from cancer therapy cause ERK1/2 to induce senescence, whereas higher doses of DNA damage fail to activate ERK1/2, and thus induce cell death by apoptosis.[13]
References
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- ^ Page Module:Citation/CS1/styles.css has no content.Rao VN, Reddy ES (July 1994). "elk-1 proteins interact with MAP kinases". Oncogene. 9 (7): 1855–60. PMID 8208531.
- ^ Page Module:Citation/CS1/styles.css has no content.Boulton TG, Cobb MH (May 1991). "Identification of multiple extracellular signal-regulated kinases (ERKs) with antipeptide antibodies". Cell Regulation. 2 (5): 357–71. doi:10.1091/mbc.2.5.357. PMC 361802. PMID 1654126.
- ^ Page Module:Citation/CS1/styles.css has no content.Leevers SJ, Marshall CJ (February 1992). "Activation of extracellular signal-regulated kinase, ERK2, by p21ras oncoprotein". The EMBO Journal. 11 (2): 569–74. doi:10.1002/j.1460-2075.1992.tb05088.x. PMC 556488. PMID 1371463.
- ^ Page Module:Citation/CS1/styles.css has no content.Kyriakis JM, App H, Zhang XF, Banerjee P, Brautigan DL, Rapp UR, Avruch J (July 1992). "Raf-1 activates MAP kinase-kinase". Nature. 358 (6385): 417–21. Bibcode:1992Natur.358..417K. doi:10.1038/358417a0. PMID 1322500. S2CID 4335307.
- ^ Page Module:Citation/CS1/styles.css has no content.Crews CM, Erikson RL (September 1992). "Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product". Proceedings of the National Academy of Sciences of the United States of America. 89 (17): 8205–9. Bibcode:1992PNAS...89.8205C. doi:10.1073/pnas.89.17.8205. PMC 49886. PMID 1381507.
- ^ Page Module:Citation/CS1/styles.css has no content.Itoh T, Kaibuchi K, Masuda T, Yamamoto T, Matsuura Y, Maeda A, Shimizu K, Takai Y (February 1993). "A protein factor for ras p21-dependent activation of mitogen-activated protein (MAP) kinase through MAP kinase kinase". Proceedings of the National Academy of Sciences of the United States of America. 90 (3): 975–9. Bibcode:1993PNAS...90..975I. doi:10.1073/pnas.90.3.975. PMC 45793. PMID 8381539.
- ^ Page Module:Citation/CS1/styles.css has no content.Yao Y, Li W, Wu J, Germann UA, Su MS, Kuida K, Boucher DM (October 2003). "Extracellular signal-regulated kinase 2 is necessary for mesoderm differentiation". Proceedings of the National Academy of Sciences of the United States of America. 100 (22): 12759–64. Bibcode:2003PNAS..10012759Y. doi:10.1073/pnas.2134254100. PMC 240691. PMID 14566055.
- ^ Page Module:Citation/CS1/styles.css has no content.Sanjo, Hideki; Hikida, Masaki; Aiba, Yuichi; Mori, Yoshiko; Hatano, Naoya; Ogata, Masato; Kurosaki, Tomohiro (2007). "Extracellular signal-regulated protein kinase 2 is required for efficient generation of B cells bearing antigen-specific immunoglobulin G". Molecular and Cellular Biology. 27 (4): 1236–1246. doi:10.1128/MCB.01530-06. ISSN 0270-7306. PMC 1800707. PMID 17145771.
- ^ Page Module:Citation/CS1/styles.css has no content.Sharp, L. L.; Schwarz, D. A.; Bott, C. M.; Marshall, C. J.; Hedrick, S. M. (1997). "The influence of the MAPK pathway on T cell lineage commitment". Immunity. 7 (5): 609–618. doi:10.1016/s1074-7613(00)80382-9. ISSN 1074-7613. PMID 9390685.
- ^ Page Module:Citation/CS1/styles.css has no content.Samuels, Ivy S.; Karlo, J. Colleen; Faruzzi, Alicia N.; Pickering, Kathryn; Herrup, Karl; Sweatt, J. David; Saitta, Sulagna C.; Landreth, Gary E. (2008-07-02). "Deletion of ERK2 mitogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function". The Journal of Neuroscience. 28 (27): 6983–6995. doi:10.1523/JNEUROSCI.0679-08.2008. ISSN 1529-2401. PMC 4364995. PMID 18596172.
- ^ Page Module:Citation/CS1/styles.css has no content.Pagès G, Guérin S, Grall D, Bonino F, Smith A, Anjuere F, Auberger P, Pouysségur J (November 1999). "Defective thymocyte maturation in p44 MAP kinase (Erk 1) knockout mice". Science. 286 (5443): 1374–7. doi:10.1126/science.286.5443.1374. PMID 10558995.
- ^ Page Module:Citation/CS1/styles.css has no content."MAPK7 mitogen-activated protein kinase 7 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-04-03.
- ^ a b Page Module:Citation/CS1/styles.css has no content.Anerillas C, Abdelmohsen K, Gorospe M (2020). "Regulation of senescence traits by MAPKs". GeroScience. 42 (2): 397–408. doi:10.1007/s11357-020-00183-3. PMC 7205942. PMID 32300964.
External links
- The Extracellular Signal-Regulated Kinases
- MAP Kinase Resource Script error: No such module "webarchive"..
- Extracellular+Signal-Regulated+MAP+Kinases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- MAPK1
- MAPK3 Info with links in the Cell Migration Gateway Script error: No such module "webarchive".
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