MAPK6: Difference between revisions

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Latest revision as of 12:50, 9 January 2019

Mitogen-activated protein kinase 6 is an enzyme that in humans is encoded by the MAPK6 gene.^[1]^[2]

The protein encoded by this gene is a member of the Ser/Thr protein kinase family, and is most closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases, also known as extracellular signal-regulated kinases (ERKs), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the nucleus, and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters.^[2]

Discovery

ERK3/MAPK6 was initially cloned from the rat brain cDNA library by homology screening with probes ERK1 derived probe.^[3]

Gene location

In humans, MAPK 6 gene is located on the distal arm of chromosome 15 (15q21.2). It is 47.01kb long and is transcribed in the centromere to telomere orientation. It consist of 6 exons with the translation initiation codon which is located in exon2.^[4]

Structure

It is an atypical member of the mitogen activated kinases family. The molecular mass of the translated protein is approximately 100kDa, and is made up of 721 amino acid residues.^[4]^[3] It contains a typical kinase domain at the N- terminal and an extended C- terminal. The first 150 residues at c- terminal are 50% similar to ERK4 protein. At the kinase domain it exhibits about 70% similarity with the ERK4 protein.^[4]^[3] The activation loop of the phosphorylation motif contains only one phospho acceptor site (Ser-Glu-Gly).^[3]

The structure is predicted by homology modelling using the crystal structure of phoshphorylated ERK2. According to the model, the structure of ERK3/MAPK6 kinase domain resembles other MAP kinases. The modelled ERK3/MAPK6 kinase domain is predicted to fold with a topology similar to other MAP kinases.^[3]

Expression

ERK3/MAPK6 is widely expressed protein however it is expressed in significantly higher amounts in skeletal muscles and brain. It is localized in cytoplasm and the nucleus of cells. ERK3/MAPK6 is a highly unstable protein and has a very little half life of less than an hour. It is degraded by ubiquitin mediated proteasomal pathway.^[4]

Function

It is very important for neonatal growth and survival. ERK3/MAPK6 forms a complex with microtubule associated protein2 (MAP2) and MAPKAPK5 which mediates the phosphorylation of MAPKAPK5 which in turn phosphorylates ERK3/MAPK6 at serine 189 residue mediating the entry into cell cycle.^[5] It also acts as a regulator for T- cell development. The catalytic activity of ERK3/MAPK6 plays an important for the proper differentiation of T-cells in the thymus. The long c- terminal is responsible for thymic differentiation.^[6]

Role in cancer

ERK3/MAPK6 interacts with and phosphorylated steroid receptor coactivator 3 (SRC-3) This coreceptor is an oncogenic protein which when overexpressed at serine 857 leads to cancer. After the phosphorylation of SRC-3 results in the upregulation of MMP activity ERK3-mediated phosphorylation at S857 was essential for interaction of SRC-3 with the ETS transcription factor PEA3, which promotes upregulation of MMP gene expression and proinvasive activity.^[7]

References

↑ Meloche, Sylvain (2005-04-01). "Erk3". AfCS-Nature Molecule Pages. doi:10.1038/mp.a000876.01. ISSN 1477-5921.
↑ ^2.0 ^2.1 "MAPK6 mitogen-activated protein kinase 6 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-11-09.
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 Coulombe P, Meloche S (August 2007). "Atypical mitogen-activated protein kinases: structure, regulation and functions". Biochimica et Biophysica Acta. 1773 (8): 1376–87. doi:10.1016/j.bbamcr.2006.11.001. PMID 17161475.
↑ ^4.0 ^4.1 ^4.2 ^4.3 "MAPK6 (mitogen-activated protein kinase 6)". atlasgeneticsoncology.org. Retrieved 2018-11-09.
↑ "Volume II Accession Number Index", Rodents, Elsevier, pp. ACCESSION–1-ACCESSION-5, 1987, ISBN 9780125125123, retrieved 2018-11-09
↑ Marquis M, Daudelin JF, Boulet S, Sirois J, Crain K, Mathien S, Turgeon B, Rousseau J, Meloche S, Labrecque N (September 2014). "The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain CD4+ CD8+ thymocyte survival". Molecular and Cellular Biology. 34 (18): 3374–87. doi:10.1128/MCB.01701-13. PMC 4135614. PMID 25002529.
↑ Long W, Foulds CE, Qin J, Liu J, Ding C, Lonard DM, Solis LM, Wistuba II, Qin J, Tsai SY, Tsai MJ, O'Malley BW (May 2012). "ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion". The Journal of Clinical Investigation. 122 (5): 1869–80. doi:10.1172/jci61492. PMC 3336992. PMID 22505454.

External links

MAP Kinase Resource .

[1] Meloche, Sylvain (2005-04-01). "Erk3". AfCS-Nature Molecule Pages. doi:10.1038/mp.a000876.01. ISSN 1477-5921.

[:0-2] 2.0 ^2.1 "MAPK6 mitogen-activated protein kinase 6 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-11-09.

[:2-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 Coulombe P, Meloche S (August 2007). "Atypical mitogen-activated protein kinases: structure, regulation and functions". Biochimica et Biophysica Acta. 1773 (8): 1376–87. doi:10.1016/j.bbamcr.2006.11.001. PMID 17161475.

[:1-4] 4.0 ^4.1 ^4.2 ^4.3 "MAPK6 (mitogen-activated protein kinase 6)". atlasgeneticsoncology.org. Retrieved 2018-11-09.

[5] "Volume II Accession Number Index", Rodents, Elsevier, pp. ACCESSION–1-ACCESSION-5, 1987, ISBN 9780125125123, retrieved 2018-11-09

[6] Marquis M, Daudelin JF, Boulet S, Sirois J, Crain K, Mathien S, Turgeon B, Rousseau J, Meloche S, Labrecque N (September 2014). "The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain CD4+ CD8+ thymocyte survival". Molecular and Cellular Biology. 34 (18): 3374–87. doi:10.1128/MCB.01701-13. PMC 4135614. PMID 25002529.

[7] Long W, Foulds CE, Qin J, Liu J, Ding C, Lonard DM, Solis LM, Wistuba II, Qin J, Tsai SY, Tsai MJ, O'Malley BW (May 2012). "ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion". The Journal of Clinical Investigation. 122 (5): 1869–80. doi:10.1172/jci61492. PMC 3336992. PMID 22505454.

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@@ Line 1: / Line 1: @@
 {{Infobox_gene}}
-'''Mitogen-activated protein kinase 6''' is an [[enzyme]] that in humans is encoded by the ''MAPK6'' [[gene]].<ref name="pmid8875998">{{cite journal |vauthors=Meloche S, Beatty BG, Pellerin J | title = Primary structure, expression and chromosomal locus of a human homolog of rat ERK3 | journal = Oncogene | volume = 13 | issue = 7 | pages = 1575–9 |date=Dec 1996 | pmid = 8875998 | pmc =  | doi =  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: MAPK6 mitogen-activated protein kinase 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5597| accessdate = }}</ref>
+'''Mitogen-activated protein kinase 6''' is an [[enzyme]] that in humans is encoded by the ''MAPK6'' [[gene]].<ref>{{Cite journal|last=Meloche|first=Sylvain|date=2005-04-01|title=Erk3|url=http://dx.doi.org/10.1038/mp.a000876.01|journal=AfCS-Nature Molecule Pages|doi=10.1038/mp.a000876.01|issn=1477-5921}}</ref><ref name=":0">{{Cite web|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5597|title=MAPK6 mitogen-activated protein kinase 6 [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|language=en|access-date=2018-11-09}}</ref>
-<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
+The protein encoded by this gene is a member of the Ser/Thr [[protein kinase]] family, and is most closely related to mitogen-activated protein kinases ([[MAP kinases]]). MAP kinases, also known as extracellular signal-regulated kinases ([[ERKs]]), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the [[Nucleus (cell)|nucleus]], and has been reported to be activated in [[fibroblasts]] upon treatment with serum or [[phorbol]] esters.<ref name=":0" />
-{{PBB_Summary
-| section_title =
-| summary_text = The protein encoded by this gene is a member of the Ser/Thr [[protein kinase]] family, and is most closely related to mitogen-activated protein kinases ([[MAP kinases]]). MAP kinases also known as extracellular signal-regulated kinases ([[ERKs]]), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the [[Nucleus (cell)|nucleus]], and has been reported to be activated in [[fibroblasts]] upon treatment with serum or [[phorbol]] esters.<ref name="entrez"/>
-}}
-==References==
+== Discovery ==
+ERK3/MAPK6 was initially cloned from the rat brain cDNA library by homology screening with probes ERK1 derived probe.<ref name=":2">{{cite journal | vauthors = Coulombe P, Meloche S | title = Atypical mitogen-activated protein kinases: structure, regulation and functions | journal = Biochimica et Biophysica Acta | volume = 1773 | issue = 8 | pages = 1376–87 | date = August 2007 | pmid = 17161475 | doi = 10.1016/j.bbamcr.2006.11.001 | url = https://doi.org/10.1016/j.bbamcr.2006.11.001 }}</ref>
+== Gene location ==
+In humans, MAPK 6 gene  is located on the distal arm of chromosome 15 (15q21.2). It is 47.01kb long and is transcribed in the centromere to telomere orientation. It consist of 6 exons with the translation initiation codon which is located in exon2.<ref name=":1">{{Cite web|url=http://atlasgeneticsoncology.org/Genes/MAPK6ID43349ch15q21.html|title=MAPK6 (mitogen-activated protein kinase 6)|website=atlasgeneticsoncology.org|access-date=2018-11-09}}</ref>
+== Structure ==
+It is an atypical member of the mitogen activated kinases family. The molecular mass of the translated protein is approximately 100kDa, and is made up of 721 amino acid residues.<ref name=":1" /><ref name=":2" /> It contains a typical kinase domain at the N- terminal and an extended C- terminal. The first 150 residues at c- terminal are 50% similar to ERK4 protein. At the kinase domain it exhibits about 70% similarity with the ERK4 protein.<ref name=":1" /><ref name=":2" /> The activation loop of the phosphorylation motif contains only one phospho acceptor site (Ser-Glu-Gly).<ref name=":2" />
+The structure is predicted by homology modelling using the crystal structure of phoshphorylated ERK2. According to the model, the structure of ERK3/MAPK6 kinase domain resembles other MAP kinases.  The modelled ERK3/MAPK6 kinase domain is predicted to fold with a topology similar to other MAP kinases.<ref name=":2" />
+== Expression ==
+ERK3/MAPK6 is widely expressed protein however it is expressed in significantly higher amounts in skeletal muscles and brain. It is localized in cytoplasm and the nucleus of cells. ERK3/MAPK6 is a highly unstable protein and has a very little half life of less than an hour. It is degraded by ubiquitin mediated proteasomal pathway.<ref name=":1" />
+== Function ==
+It is very important for neonatal growth and survival. ERK3/MAPK6 forms a complex with microtubule associated protein2 (MAP2) and MAPKAPK5 which mediates the phosphorylation of MAPKAPK5 which in turn phosphorylates ERK3/MAPK6 at serine 189 residue mediating the entry into cell cycle.<ref>{{Citation|title=Volume II Accession Number Index|date=1987|url=http://dx.doi.org/10.1016/b978-0-12-512512-3.50015-8|work=Rodents|pages=ACCESSION–1-ACCESSION-5|publisher=Elsevier|isbn=9780125125123|access-date=2018-11-09}}</ref> It also acts as a regulator for T- cell development. The  catalytic  activity of ERK3/MAPK6 plays an important for the proper differentiation of T-cells in the thymus. The long c- terminal is responsible for thymic differentiation.<ref>{{cite journal | vauthors = Marquis M, Daudelin JF, Boulet S, Sirois J, Crain K, Mathien S, Turgeon B, Rousseau J, Meloche S, Labrecque N | title = The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain CD4+ CD8+ thymocyte survival | journal = Molecular and Cellular Biology | volume = 34 | issue = 18 | pages = 3374–87 | date = September 2014 | pmid = 25002529 | pmc = 4135614 | doi = 10.1128/MCB.01701-13 | url = https://mcb.asm.org/content/34/18/3374 }}</ref>
+== Role in cancer ==
+ERK3/MAPK6  interacts with and phosphorylated steroid receptor coactivator 3 (SRC-3) This coreceptor   is an oncogenic protein which when overexpressed at serine 857 leads to cancer. After the phosphorylation of  SRC-3 results in the upregulation of  MMP activity ERK3-mediated phosphorylation at S857 was essential for interaction of SRC-3 with the ETS transcription factor PEA3, which promotes upregulation of MMP gene expression and proinvasive activity.<ref>{{cite journal | vauthors = Long W, Foulds CE, Qin J, Liu J, Ding C, Lonard DM, Solis LM, Wistuba II, Qin J, Tsai SY, Tsai MJ, O'Malley BW | title = ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion | journal = The Journal of Clinical Investigation | volume = 122 | issue = 5 | pages = 1869–80 | date = May 2012 | pmid = 22505454 | pmc = 3336992 | doi = 10.1172/jci61492 | url = https://doi.org/10.1172/JCI61492 }}</ref>
+== References ==
 {{reflist}}
-==External links==
+== Further reading ==
-* [http://www.mapkinases.eu MAP Kinase Resource ].
-==Further reading==
 {{refbegin | 2}}
-{{PBB_Further_reading
+* {{cite journal | vauthors = Boulton TG, Nye SH, Robbins DJ, Ip NY, Radziejewska E, Morgenbesser SD, DePinho RA, Panayotatos N, Cobb MH, Yancopoulos GD | title = ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF | journal = Cell | volume = 65 | issue = 4 | pages = 663–75 | date = May 1991 | pmid = 2032290 | doi = 10.1016/0092-8674(91)90098-J }}
-| citations =
+* {{cite journal | vauthors = Zhu AX, Zhao Y, Moller DE, Flier JS | title = Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3 | journal = Molecular and Cellular Biology | volume = 14 | issue = 12 | pages = 8202–11 | date = December 1994 | pmid = 7969157 | pmc = 359359 | doi =  }}
-*{{cite journal  | author=Boulton TG |title=ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF |journal=Cell |volume=65 |issue= 4 |pages= 663–675 |year= 1991 |pmid= 2032290 |doi=10.1016/0092-8674(91)90098-J  |name-list-format=vanc| author2=Nye SH  | author3=Robbins DJ  | display-authors=3  | last4=Ip  | first4=Nancy Y.  | last5=Radzlejewska  | first5=Elizabeth  | last6=Morgenbesser  | first6=Sharon D.  | last7=Depinho  | first7=Ronald A.  | last8=Panayotatos  | first8=Nikos  | last9=Cobb  | first9=Melanie H.  }}
+* {{cite journal | vauthors = Cheng M, Boulton TG, Cobb MH | title = ERK3 is a constitutively nuclear protein kinase | journal = The Journal of Biological Chemistry | volume = 271 | issue = 15 | pages = 8951–8 | date = April 1996 | pmid = 8621539 | doi = 10.1074/jbc.271.15.8951 }}
-*{{cite journal  |vauthors=Zhu AX, Zhao Y, Moller DE, Flier JS |title=Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3 |journal=Mol. Cell. Biol. |volume=14 |issue= 12 |pages= 8202–11 |year= 1994 |pmid= 7969157 |doi=  | pmc=359359  }}
+* {{cite journal | vauthors = Sauma S, Friedman E | title = Increased expression of protein kinase C beta activates ERK3 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 19 | pages = 11422–6 | date = May 1996 | pmid = 8626698 | doi = 10.1074/jbc.271.19.11422 }}
-*{{cite journal  |vauthors=Cheng M, Boulton TG, Cobb MH |title=ERK3 is a constitutively nuclear protein kinase |journal=J. Biol. Chem. |volume=271 |issue= 15 |pages= 8951–8958 |year= 1996 |pmid= 8621539 |doi=10.1074/jbc.271.15.8951  }}
+* {{cite journal | vauthors = Zimmermann J, Lamerant N, Grossenbacher R, Furst P | title = Proteasome- and p38-dependent regulation of ERK3 expression | journal = The Journal of Biological Chemistry | volume = 276 | issue = 14 | pages = 10759–66 | date = April 2001 | pmid = 11148204 | doi = 10.1074/jbc.M008567200 }}
-*{{cite journal  |vauthors=Sauma S, Friedman E |title=Increased expression of protein kinase C beta activates ERK3 |journal=J. Biol. Chem. |volume=271 |issue= 19 |pages= 11422–11426 |year= 1996 |pmid= 8626698 |doi=10.1074/jbc.271.19.11422  }}
+* {{cite journal | vauthors = Robinson MJ, Xu Be BE, Stippec S, Cobb MH | title = Different domains of the mitogen-activated protein kinases ERK3 and ERK2 direct subcellular localization and upstream specificity in vivo | journal = The Journal of Biological Chemistry | volume = 277 | issue = 7 | pages = 5094–100 | date = February 2002 | pmid = 11741894 | doi = 10.1074/jbc.M110935200 }}
-*{{cite journal  |vauthors=Zimmermann J, Lamerant N, Grossenbacher R, Furst P |title=Proteasome- and p38-dependent regulation of ERK3 expression |journal=J. Biol. Chem. |volume=276 |issue= 14 |pages= 10759–10766 |year= 2001 |pmid= 11148204 |doi= 10.1074/jbc.M008567200 }}
+* {{cite journal | vauthors = Kinet S, Bernard F, Mongellaz C, Perreau M, Goldman FD, Taylor N | title = gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4(+) lymphocytes | journal = Blood | volume = 100 | issue = 7 | pages = 2546–53 | date = October 2002 | pmid = 12239168 | doi = 10.1182/blood-2002-03-0819 }}
-*{{cite journal  |vauthors=Robinson MJ, Xu Be BE, Stippec S, Cobb MH |title=Different domains of the mitogen-activated protein kinases ERK3 and ERK2 direct subcellular localization and upstream specificity in vivo |journal=J. Biol. Chem. |volume=277 |issue= 7 |pages= 5094–5100 |year= 2002 |pmid= 11741894 |doi= 10.1074/jbc.M110935200 }}
+* {{cite journal | vauthors = Coulombe P, Rodier G, Pelletier S, Pellerin J, Meloche S | title = Rapid turnover of extracellular signal-regulated kinase 3 by the ubiquitin-proteasome pathway defines a novel paradigm of mitogen-activated protein kinase regulation during cellular differentiation | journal = Molecular and Cellular Biology | volume = 23 | issue = 13 | pages = 4542–58 | date = July 2003 | pmid = 12808096 | pmc = 164847 | doi = 10.1128/MCB.23.13.4542-4558.2003 }}
-*{{cite journal  | author=Kinet S |title=gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4(+) lymphocytes |journal=Blood |volume=100 |issue= 7 |pages= 2546–2553 |year= 2002 |pmid= 12239168 |doi= 10.1182/blood-2002-03-0819  |name-list-format=vanc| author2=Bernard F  | author3=Mongellaz C  | display-authors=3  | last4=Perreau  | first4=M  | last5=Goldman  | first5=FD  | last6=Taylor  | first6=N }}
+* {{cite journal | vauthors = Julien C, Coulombe P, Meloche S | title = Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progression | journal = The Journal of Biological Chemistry | volume = 278 | issue = 43 | pages = 42615–24 | date = October 2003 | pmid = 12915405 | doi = 10.1074/jbc.M302724200 }}
-*{{cite journal  | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–16903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241  |name-list-format=vanc| author2=Feingold EA  | author3=Grouse LH  | display-authors=3  | last4=Derge  | first4=JG  | last5=Klausner  | first5=RD  | last6=Collins  | first6=FS  | last7=Wagner  | first7=L  | last8=Shenmen  | first8=CM  | last9=Schuler  | first9=GD }}
+* {{cite journal | vauthors = Rai R, Mahale A, Saranath D | title = Molecular cloning, isolation and characterisation of ERK3 gene from chewing-tobacco induced oral squamous cell carcinoma | journal = Oral Oncology | volume = 40 | issue = 7 | pages = 705–12 | date = August 2004 | pmid = 15172640 | doi = 10.1016/j.oraloncology.2004.01.010 }}
-*{{cite journal  | author=Coulombe P |title=Rapid turnover of extracellular signal-regulated kinase 3 by the ubiquitin-proteasome pathway defines a novel paradigm of mitogen-activated protein kinase regulation during cellular differentiation |journal=Mol. Cell. Biol. |volume=23 |issue= 13 |pages= 4542–4558 |year= 2003 |pmid= 12808096 |doi=10.1128/MCB.23.13.4542-4558.2003  | pmc=164847  |name-list-format=vanc| author2=Rodier G  | author3=Pelletier S  | display-authors=3  | last4=Pellerin  | first4=J.  | last5=Meloche  | first5=S.  }}
+* {{cite journal | vauthors = Coulombe P, Rodier G, Bonneil E, Thibault P, Meloche S | title = N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasome | journal = Molecular and Cellular Biology | volume = 24 | issue = 14 | pages = 6140–50 | date = July 2004 | pmid = 15226418 | pmc = 434260 | doi = 10.1128/MCB.24.14.6140-6150.2004 }}
-*{{cite journal  |vauthors=Julien C, Coulombe P, Meloche S |title=Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progression |journal=J. Biol. Chem. |volume=278 |issue= 43 |pages= 42615–42624 |year= 2004 |pmid= 12915405 |doi= 10.1074/jbc.M302724200 }}
+* {{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
-*{{cite journal  |vauthors=Rai R, Mahale A, Saranath D |title=Molecular cloning, isolation and characterisation of ERK3 gene from chewing-tobacco induced oral squamous cell carcinoma |journal=Oral Oncol. |volume=40 |issue= 7 |pages= 705–712 |year= 2004 |pmid= 15172640 |doi= 10.1016/j.oraloncology.2004.01.010 }}
+* {{cite journal | vauthors = Hoeflich KP, Eby MT, Forrest WF, Gray DC, Tien JY, Stern HM, Murray LJ, Davis DP, Modrusan Z, Seshagiri S | title = Regulation of ERK3/MAPK6 expression by BRAF | journal = International Journal of Oncology | volume = 29 | issue = 4 | pages = 839–49 | date = October 2006 | pmid = 16964379 | doi = 10.3892/ijo.29.4.839 }}
-*{{cite journal  | author=Coulombe P |title=N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasome |journal=Mol. Cell. Biol. |volume=24 |issue= 14 |pages= 6140–6150 |year= 2004 |pmid= 15226418 |doi= 10.1128/MCB.24.14.6140-6150.2004  | pmc=434260  |name-list-format=vanc| author2=Rodier G  | author3=Bonneil E  | display-authors=3  | last4=Thibault  | first4=P.  | last5=Meloche  | first5=S. }}
-*{{cite journal  | author=Gerhard DS |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–2127 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928  |name-list-format=vanc| author2=Wagner L  | author3=Feingold EA  | display-authors=3  | last4=Shenmen  | first4=CM  | last5=Grouse  | first5=LH  | last6=Schuler  | first6=G  | last7=Klein  | first7=SL  | last8=Old  | first8=S  | last9=Rasooly  | first9=R }}
-*{{cite journal  | author=Rual JF |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=Nature |volume=437 |issue= 7062 |pages= 1173–1178 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209  |name-list-format=vanc| author2=Venkatesan K  | author3=Hao T  | display-authors=3  | last4=Hirozane-Kishikawa  | first4=Tomoko  | last5=Dricot  | first5=Amélie  | last6=Li  | first6=Ning  | last7=Berriz  | first7=Gabriel F.  | last8=Gibbons  | first8=Francis D.  | last9=Dreze  | first9=Matija }}
-*{{cite journal  | author=Hoeflich KP |title=Regulation of ERK3/MAPK6 expression by BRAF |journal=Int. J. Oncol. |volume=29 |issue= 4 |pages= 839–49 |year= 2006 |pmid= 16964379 |doi=  10.3892/ijo.29.4.839|name-list-format=vanc| author2=Eby MT  | author3=Forrest WF  | display-authors=3  | last4=Gray  | first4=DC  | last5=Tien  | first5=JY  | last6=Stern  | first6=HM  | last7=Murray  | first7=LJ  | last8=Davis  | first8=DP  | last9=Modrusan  | first9=Z  }}
-}}
 {{refend}}
+== External links ==
+* [http://www.mapkinases.eu MAP Kinase Resource ].
 {{PDB Gallery|geneid=5597}}
@@ Line 40: / Line 55: @@
 {{Enzymes}}
 {{Portal bar|Molecular and Cellular Biology|border=no}}
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 [[Category:EC 2.7.11]]
-{{gene-15-stub}}

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)