Mitogen-activated protein kinase

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[[Image:1erk.png|left|thumb|300px|Crystal Structure of the Mitogen-activated protein kinase, [[1erk]]]]
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<StructureSection load='' size='350' side='right' caption='Human MAPK1 complex with inhibitor and sulfate (PDB entry [[2ojg]])' scene='43/438476/Cv/2'>
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{{STRUCTURE_1erk| right| PDB=1erk | SCENE=Mitogen-activated_protein_kinase/Cv/1 |CAPTION=Mitogen-activated protein kinase, [[1erk]] }}
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== Function ==
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[[Mitogen-activated protein kinase]] (MAPK) also known as '''Extracellular Signal-Regulated Kinase (ERK)''' are serine/threonine kinases which regulate various cellular activities in response to extracellular stimuli by mitogens, heat shock and more. MAPK is part of the MAPK cascade which consists of MAPK, [[Mitogen-activated protein kinase kinase|MAP2K]] and [[Mitogen-activated protein kinase kinase kinase|MAP3K]] which are activated by phosphorylation<ref>PMID:9069255</ref>. <br />
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See also [[Mitogen-activated protein kinase cascade]].
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* '''MAPK1''' or '''ERK2''' and '''MAPK3''' are activated in response to growth factors. For '''MAPK1''' representations see [[Michael Roberts/BIOL115/ERK2]].<br />
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* '''MAPK6''' is activated by phorbol esters.<br />
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* '''MAPK7''' is activated by stress stimuli.<br />
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* '''MAPK8 (called also c-Jun N-terminal kinase 1 or JNK1), MAPK9, MAPK10''' (called also c-Jun N-terminal kinase 3 or JNK3), '''MAPK11, MAPK12, MAPK13, MAPK14''' are stress-activated.<br />
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* '''MAPK11''' (also called '''p38-β MAPK'''), '''MAPK12''' (also called '''p38-γ MAPK'''), '''MAPK13''' (also called '''p38-δ MAPK'''), '''MAPK14''' (also called '''p38-α MAPK''') belongs to the class called [[UMass Chem 423 Student Projects 2011-2#p38 kinase|p38 MAPK (UMass Chem 423 Student Projects 2011-2)]].
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== Relevance ==
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MAPK cascade is elevated in cancer cells, hence MAPK inhibitors are tested as potential cancer therapy.
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== Disease ==
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MAPK14 is associated with acquired hyperkeratosis and prostate transitional cell carcinoma.
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== Structural highlights ==
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<scene name='43/438476/Cv/5'>Inhibitors of MAPK bind in its ATP-binding site</scene><ref>PMID:17300186</ref>. Water molecule are shown as red sphere.
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[[Mitogen-activated protein kinase]] (MAPK) also known as Extracellular Signal-Regulated Kinase (ERK) are serine/threonine kinases which regulate various cellular activities in response to extracellular stimuli by mitogens, heat shock and more. MAPK is part of the MAPK cascade which consists of MAPK, [[Mitogen-activated protein kinase kinase|MAP2K]] and [[Mitogen-activated protein kinase kinase kinase|MAP3K]] which are activated by phosphorylation. MAPK1 and MAPK3 are activated in response to growth factors. For MAPK2 representations see [[Michael Roberts/BIOL115/ERK2]]. MAPK6 is activated by phorbol esters. MAPK7 is activated by stress stimuli. MAPK8, MAPK9, MAPK10 (called also c-Jun N-terminal kinase 3 or JNK3), MAPK11, MAPK12, MAPK13, MAPK14 are stress-activated. MAPK11, MAPK12, MAPK13, MAPK14 belong to the class called p38 MAPK. images on the left and right correspond to one representative MAPK structure, ''i.e.'' the rat MAPK1 ([[1erk]]).
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{{TOC limit|limit=2}}
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== 3D Structures of Mitogen-activated protein kinase ==
== 3D Structures of Mitogen-activated protein kinase ==
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[[Mitogen-activated protein kinase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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===MAPK1===
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[[3i5z]], [[3i60]], [[2e14]], [[2ojg]], [[2oji]], [[2ojj]], [[1wzy]], [[1tvo]] – hMAPK1+inhibitor - human<br />
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[[2z7l]], [[3c9w]], [[3qyw]], [[3qyz]] - rMAPK1+inhibitor – rat<br />
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[[1erk]] - rMAPK1<br />
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[[1gol]], [[3r63]] - rMAPK1 (mutant)<br />
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[[2gph]] - rMAPK1 (mutant)+HEPTP (mutant)<br />
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[[3o71]] - rMAPK1 + colorectal cancer peptide<br />
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[[2fys]] - rMAPK1 + KIM peptide<br />
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[[2y4i]] – raMAPK1+kinase suppressor of RAS 2 – rabbit<br />
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[[3oz6]] - MAPK1 - Cryptosporidium parvum
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===MAPK2===
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[[3gok]] - hMAPK2 kinase domain<br />
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[[2pzy]], [[2p3g]], [[2jbo]], [[2jbp]] – hMAPK2+inhibitor<br />
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[[3a2c]], [[3kc3]], [[3fpm]], [[3fyj]], [[3fyk]] - hMAPK2 kinase domain +inhibitor<br />
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[[3m2w]], [[3kga]], [[3ka0]] – hMAPK2 kinase domain (mutant)+inhibitor<br />
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[[2oza]], [[2okr]], [[2onl]] – hMAPK2+ hMAPK14<br />
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[[2npt]] - hMAPK2+ hMAPK5<br />
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[[2erk]] – rMAPK2<br />
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[[3erk]], [[4erk]] – rMAPK2+inhibitor<br />
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===MAPK3===
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[[2zoq]] – hMAPK3<br />
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===MAPK6===
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[[3fxw]], [[3fhr]] – hMAPK3 kinase domain +inhibitor<br />
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[[2i6l]] – hMAPK6<br />
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===MAPK7===
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[[2q8y]] - MAPK7+Virulence protein
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===MAPK8===
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[[3o17]], [[2gmx]], [[2g01]] – hMAPK8 (mutant)+JIP1 peptide<br />
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[[1ukh]], [[1uki]] - jMAPK8 JNK1+JIP1 peptide<br />
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[[3o2m]] - hMAPK8 (mutant)+JIP1 peptide+biaryl tetrazole<br />
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[[2xrw]], [[2xs0]] - hMAPK8 + NFAT peptide<br />
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[[3elj]] - hMAPK8+inhibitor<br />
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[[2no3]], [[2h96]] – hMAPK8 (mutant)+inhibitor<br />
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===MAPK9===
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[[3e7o]] - hMAPK9 (mutant)<br />
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[[3npc]] – hMAPK9 (mutant)+inhibitor<br />
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===MAPK10===
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[[3kvx]], [[3fv8]], [[2waj]], [[3fi2]], [[3fi3]], [[3da6]], [[2zdt]], [[2zdu]], [[3cgf]], [[3cgo]], [[2r9s]], [[2o0u]], [[2o2u]], [[2exc]], [[2b1p]], [[1pmn]], [[1pmq]], [[1pmu]], [[1pmv]], [[3oy1]], [[2ok1]], [[3ttj]], [[3tti]], – hMAPK10+inhibitor<br />
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[[3ptg]], [[4h39]] - hMAPK10 catalytic domain + JIP1 peptide <br />
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[[4h36]] – hMAPK10 catalytic domain + ATF2 peptide<br />
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[[4h3b]] – hMAPK10 catalytic domain + SAB peptide<br />
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[[1jnk]] – hMAPK10 catalytic domain + AMPPNP<br />
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[[3g9l]], [[3g90]], [[3g9n]], [[2p33]] – hMAPK10 catalytic domain+inhibitor<br />
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[[3oxi]] - hMAPK10 + MAPK8 interacting protein + inhibitor<br />
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===MAPK11===
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[[3gp0]] – hMAPK11+inhibitor<br />
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[[3gc8]], [[3gc9]] – hMAPK11 (mutant)+inhibitor<br />
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===MAPK13===
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[[3coi]] – hMAPK13<br />
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===MAPK14===
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[[3mgy]], [[3mh0]], [[3mh1]], [[3mh2]], [[3mh3]], [[3hvc]], [[3npq]], [[1wbo]], [[1r39]], [[2npq]] – hMAPK14<br />
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[[3od6]], [[3ody]], [[3odz]], [[3oef]], [[3p4k]], [[2fsl]], [[2fsm]], [[2fso]], [[2fst]], [[1r3c]] – hMAPK14 (mutant)<br />
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[[3new]], [[3ocg]], [[3mvl]], [[3mvm]], [[3nnu]], [[3nnv]], [[3nnw]], [[3nnx]], [[3nww]], [[3mpt]], [[3lhj]], [[3huc]], [[3itz]], [[3l8x]], [[3kf7]], [[3fi4]], [[3fkl]], [[3fkn]], [[3fko]], [[3fl4]], [[3fln]], [[3flq]], [[3fls]], [[3flw]], [[3fly]], [[3flz]], [[3fmh]], [[3fmj]], [[3fmk]], [[3fml]], [[3flm]], [[3fln]], [[3fsf]], [[3fsk]], [[3kq7]], [[3iph]], [[3hv4]], [[3hv5]], [[3hv6]], [[3hv7]], [[3k3i]], [[3hec]], [[3heg]], [[3gi3]], [[3hp2]], [[3hp5]], [[3hrb]], [[3ha8]], [[3gfe]], [[3hl7]], [[3hll]], [[3gcu]], [[3fc1]], [[3dt1]], [[3e92]], [[3e93]], [[3d7z]], [[3d83]], [[3ctq]], [[2puu]], [[3bx5]], [[3c5u]], [[2zaz]], [[2zb0]], [[2zb1]], [[2qd9]], [[2ewa]], [[2gfs]], [[2baj]], [[2bak]], [[2bal]], [[2baq]], [[1zyj]], [[1wbn]], [[1wbs]], [[1wbt]], [[1wbv]], [[1wbw]], [[1zz2]], [[1zzl]], [[1yqj]], [[1w7h]], [[1w82]], [[1w83]], [[1w84]], [[1oz1]], [[1ouk]], [[1ouy]], [[1m7q]], [[1kv1]], [[1kv2]], [[1di9]], [[2rg5]], [[2rg6]], [[3bv3]], [[3bv2]], [[3fmm]], [[3fmn]], [[3lfa]], [[3mw1]], [[3pg3]], [[3roc]] - hMAPK14+inhibitor<br />
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[[3o8t]], [[3mpa]], [[3obg]], [[3o8u]], [[3o8p]], [[3obj]], [[3oc1]], [[3hub]], [[3l8s]], [[3hv3]], [[3iw5]], [[3iw6]], [[3iw7]], [[3iw8]], [[3k3j]], [[3gc7]], [[3gcp]], [[3gcq]], [[3gcs]], [[3gcv]], [[3ds6]], [[2i0h]], [[1ove]], [[3lfb]], [[3lfc]], [[3lfd]], [[3lfe]], [[3lff]] - hMAPK14 (mutant)+inhibitor<br />
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[[2gtn]], [[2gtm]], [[3p5k]], [[3p78]], [[3p79]], [[3p7a]], [[3p7b]], [[3p7c]] - mMAPK14+inhibitor<br />
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[[2ghm]], [[2ghl]], [[1ywr]] - mMAPK14 (mutant)+inhibitor<br />
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[[3py3]] - mMAPK14 phosphorylated<br />
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[[1yw2]] - mMAPK14 (mutant)<br />
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[[1lew]] - mMAPK14+MEF2A<br />
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[[1lez]] - mMAPK14+MKK3B<br />
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===MAPK p38===
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[[1wfc]] - hMAPK p38<br />
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[[1bl6]], [[1bl7]], [[1bmk]], [[1a9u]], [[1ian]] – hMAPK p38 (mutant)+inhibitor<br />
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[[1p38]] - mMAPK p38 (mutant) - mouse<br />
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===MAPK FUSS===
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[[2f9g]], [[2b9f]] – yMAPK FUSS – yeast<br />
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[[2fa2]] – yMAPK FUSS (mutant)<br />
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[[2f49]] - yMAPK FUSS+STE5 peptide<br />
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[[2b9h]], [[2b9i]] - yMAPK FUSS (mutant)+MSG5 peptide<br />
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[[2b9j]] - yMAPK FUSS (mutant)+FAR1 peptide<br />
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[[3rp9]] – MAPK – ''Toxoplasma gondii''
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human MAPK1 complex with inhibitor and sulfate (PDB entry 2ojg)

Drag the structure with the mouse to rotate

References

  1. ↑ Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol. 1997 Apr;9(2):180-6. PMID:9069255
  2. ↑ Aronov AM, Baker C, Bemis GW, Cao J, Chen G, Ford PJ, Germann UA, Green J, Hale MR, Jacobs M, Janetka JW, Maltais F, Martinez-Botella G, Namchuk MN, Straub J, Tang Q, Xie X. Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors. J Med Chem. 2007 Mar 22;50(6):1280-7. Epub 2007 Feb 15. PMID:17300186 doi:http://dx.doi.org/10.1021/jm061381f

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

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