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Mitogen-activated protein kinase

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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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<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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== 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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[[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. <br />
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See also [[Mitogen-activated protein kinase cascade]].
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* '''MAPK1''' and '''MAPK3''' are activated in response to growth factors.<br />
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* For '''MAPK2''' representations see [[Michael Roberts/BIOL115/ERK2]].<br />
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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 />
* '''MAPK6''' is activated by phorbol esters.<br />
* '''MAPK6''' is activated by phorbol esters.<br />
* '''MAPK7''' is activated by stress stimuli.<br />
* '''MAPK7''' is activated by stress stimuli.<br />
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* '''MAPK8, MAPK9, MAPK10''' (called also c-Jun N-terminal kinase 3 or JNK3), '''MAPK11, MAPK12, MAPK13, MAPK14''' are stress-activated.<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) belong to the class called p38 MAPK.
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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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== 3D Structures of Mitogen-activated protein kinase ==
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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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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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== Disease ==
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{{#tree:id=OrganizedByTopic|openlevels=0|
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MAPK14 is associated with acquired hyperkeratosis and prostate transitional cell carcinoma.
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*MAPK1
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== Structural highlights ==
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**[[4g6n]], [[4g6o]], [[4gsb]] – hMAPK1 - human<br />
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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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**[[3i5z]], [[3i60]], [[2e14]], [[2ojg]], [[2oji]], [[2ojj]], [[1wzy]], [[1tvo]], [[3sa0]], [[4fux]], [[4fuy]], [[4fv0]], [[4fv1]], [[4fv2]], [[4fv3]], [[4fv4]], [[4fv5]], [[4fv6]], [[4fv7]], [[4fv8]], [[4fv9]] – hMAPK1+inhibitor - human<br />
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**[[2y9q]] – hMAPK1 + MAP kinase-interacting Ser/Thr protein kinase peptide<br />
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**[[3tei]] – hMAPK1 (mutant) + ribosomal protein S6 kinase α-1<br />
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**[[4iz5]], [[4iz7]], [[4iza]] – hMAPK1 (mutant) + astrocytic phosphoprotein <br />
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**[[4fmq]] – hMAPK1 + MAPK docking peptide<br />
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**[[4h3q]] – hMAPK1 + MAP2K 2 peptide<br />
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**[[2z7l]], [[3c9w]], [[3qyw]], [[3qyz]], [[3qyi]] - 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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**[[4gt3]], [[4gva]] – rMAPK1 + nucleotide<br />
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**[[4i5h]] – rMAPK1 (mutant) + inhibitor<br />
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**[[3o71]] - rMAPK1 + colorectal cancer peptide<br />
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**[[3zu7]], [[3zuv]] – rMAPK1 + ankyrin repeat protein<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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== 3D Structures of Mitogen-activated protein kinase ==
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[[Mitogen-activated protein kinase 3D structures]]
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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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**[[4ic8]] – hMAPK7<br />
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**[[4b99]] – hMAPK7+inhibitor<br />
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**[[4ic7]] – hMAPK7+ MAP2K 5<br />
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*MAPK8
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**[[3o17]], [[2gmx]], [[2g01]], [[3vud]], [[3vug]], [[3vuh]], [[3vui]], [[3vuk]], [[3vul]], [[3vum]] – hMAPK8 (mutant)+JIP1 peptide<br />
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**[[1ukh]], [[1uki]] - jMAPK8 JNK1+JIP1 peptide<br />
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**[[3v3v]] - hMAPK8 JNK1+JIP1 peptide + quercedagetin<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]], [[3pze]], [[4awi]], [[4l7f]] - hMAPK8+inhibitor<br />
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**[[4e73]], [[4g1w]], [[4hys]], [[4hyu]], [[4izy]] – hMAPK8 + JIP1 +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]], [[3rtp]], [[3v6r]], [[3v6s]] – 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]], [[4exu]] – hMAPK13<br />
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**[[4eyj]], [[4eym]] - hMAPK13 +inhibitor<br />
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*MAPK14
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**[[3mgy]], [[3mh0]], [[3mh1]], [[3mh2]], [[3mh3]], [[3hvc]], [[3npq]], [[1wbo]], [[1r39]], [[2npq]], [[1wfc]], [[1cm8]] – hMAPK14<br />
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**[[2lgc]] – hMAPK14 – NMR<br />
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**[[3od6]], [[3ody]], [[3odz]], [[3oef]], [[3p4k]], [[2fsl]], [[2fsm]], [[2fso]], [[2fst]], [[1r3c]], [[4e5a]], [[4geo]] – 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]] ,[[2yis]], [[2yiw]], [[2yix]], [[3qud]], [[3que]], [[3rin]], [[3s3i]], [[3s4q]], [[3u8w]], [[3uvp]], [[3uvq]], [[3uvr]], [[3zs5]], [[3zsg]], [[3zsh]], [[3zsi]], [[3zya]], [[4a9y]], [[4aa0]], [[4aa4]], [[4aa5]], [[4aac]], [[4dli]], [[4dlj]], [[4e5b]], [[4eh2]], [[4eh3]], [[4eh4]], [[4eh5]], [[4eh6]], [[4eh7]], [[4eh8]], [[4eh9]], [[4ehv]], [[4ewq]], [[4f9w]], [[4f9y]], [[4fa2]], [[4kin]], [[4kip]], [[4kiq]], [[4l8m]] - hMAPK14+inhibitor<br />
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**[[4e6a]], [[4e6c]], [[4e8a]] - hMAPK14+ lipid<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]], [[1bl6]], [[1bl7]], [[1bmk]], [[1a9u]], [[1ian]] - hMAPK14 (mutant)+inhibitor<br />
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**[[2y8o]] – hMAPK14 (mutant) + dual specificity MAP2K peptide<br />
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**[[4ka3]], [[4loo]], [[4lop]], [[4loq]] – hMAPK14 + docking peptide<br />
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**[[3tg1]] – hMAPK14 + MAPK phosphatase 5<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]], [[1p38]] - mMAPK14 (mutant)<br />
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**[[1lew]] - mMAPK14+MEF2A<br />
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**[[1lez]] - mMAPK14+MKK3B<br />
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*MAPK Fus3
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**[[2f9g]], [[2b9f]] – yMAPK Fus3 – yeast<br />
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**[[2fa2]] – yMAPK Fus3 (mutant)<br />
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**[[2f49]] - yMAPK Fus3 +STE5 peptide<br />
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**[[2b9h]], [[2b9i]] - yMAPK Fus3 (mutant)+MSG5 peptide<br />
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**[[2b9j]] - yMAPK Fus3 (mutant)+FAR1 peptide<br />
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*MAPK
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</StructureSection>
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**[[3rp9]] – MAPK – ''Toxoplasma gondii''<br />
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== References ==
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**[[3uib]] – MAPK + inhibitor – ''Leishmania major''<br />
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<references/>
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}}
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[[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

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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