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. 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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== 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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