Mitogen-activated protein kinase: Difference between revisions

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<StructureSection load='2ojg' size='350' side='right' caption='Human MAPK1 complex with inhibitor and sulfate (PDB entry [[2ojg]])' scene='43/438476/Cv/2'>
<StructureSection load='' size='350' side='right' caption='Human MAPK1 complex with inhibitor and sulfate (PDB entry [[2ojg]])' scene='43/438476/Cv/2'>
== Function ==
== Function ==
[[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 />
[[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 />
See also [[Mitogen-activated protein kinase cascade]].
* '''MAPK1''' or '''ERK2''' and '''MAPK3''' are activated in response to growth factors.  For '''MAPK1''' representations see [[Michael Roberts/BIOL115/ERK2]].<br />
* '''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 />
*  '''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 />
*  '''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 />
* '''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 p38 MAPK.
* '''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)]].  


== Relevance ==
== Relevance ==
Line 15: Line 18:


== Structural highlights ==
== Structural highlights ==
<scene name='43/438476/Cv/4'>Inhibitors of MAPK bind in its ATP-binding site</scene><ref>PMID:17300186</ref>. Water molecule shown as red sphere.  
<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.  
</StructureSection>


== 3D Structures of Mitogen-activated protein kinase ==
== 3D Structures of Mitogen-activated protein kinase ==
[[Mitogen-activated protein kinase 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*MAPK1
**[[4g6n]], [[4g6o]], [[4gsb]] – hMAPK1 - human<br />
**[[3i5z]], [[3i60]], [[3w55]], [[2ojg]], [[2oji]], [[2ojj]], [[1wzy]], [[1tvo]], [[3sa0]], [[4fux]], [[4fuy]], [[4fv0]], [[4fv1]], [[4fv2]], [[4fv3]], [[4fv4]], [[4fv5]], [[4fv6]], [[4fv7]], [[4fv8]], [[4fv9]], [[4n4s]], [[4o6e]], [[4qp1]], [[4qp2]], [[4qp3]], [[4qp4]], [[4qp6]], [[4qp7]], [[4qp8]], [[4qp9]] [[4qpa]], [[4qta]], [[4qte]], [[4xj0]], [[4xne]], [[4xoy]], [[4xoz]], [[4xp0]], [[4xp2]], [[4xp3]], [[4xrj]], [[4xrl]], [[4zzm]], [[4zzn]], [[4zzo]], [[5bue]], [[5bui]], [[5buj]], [[5bvd]], [[5bve]], [[5bvf]], [[5hd4]], [[5hd7]], [[5k4i]], [[5ke0]], [[5lcj]], [[5lck]], [[5ngu]], [[5nhf]], [[5nhh]], [[5nhj]], [[5nhl]], [[5nho]], [[5nhp]], [[5nhv]], [[5u6i]] – hMAPK1+inhibitor - human<br />
**[[2y9q]] – hMAPK1 + MAP kinase-interacting Ser/Thr protein kinase peptide<br />
**[[3tei]], [[4h3p]], [[4nif]] – hMAPK1 (mutant) + ribosomal protein S6 kinase α-1<br />
**[[4iz5]], [[4iz7]], [[4iza]] – hMAPK1 (mutant) + astrocytic phosphoprotein <br />
**[[4fmq]] – hMAPK1 + MAPK docking peptide<br />
**[[4h3q]] – hMAPK1 + MAP2K 2 peptide<br />
**[[5ax3]] – hMAPK1 + allosteric inhibitor peptide<br />
**[[4n0s]] – hMAPK1 + cafeic acid<br />
**[[4zxt]] – hMAPK1 + catechol<br />
**[[2z7l]], [[3c9w]], [[3qyw]], [[3qyz]], [[4qyy]] - rMAPK1+inhibitor – rat<br />
**[[1erk]], [[4s31]], [[5umo]] - rMAPK1<br />
**[[1gol]], [[3r63]], [[4s2z]], [[4s30]] - rMAPK1 (mutant)<br />
**[[2gph]] - rMAPK1 (mutant)+HEPTP (mutant)<br />
**[[3o71]] - rMAPK1 + colorectal cancer peptide<br />
**[[2fys]] - rMAPK1 + KIM peptide<br />
**[[4s32]] – rMAPK1 + AMPPNP<br />
**[[4s33]], [[4s34]] – rMAPK1 (mutant) + AMPPNP<br />
**[[4gt3]], [[4gva]] – rMAPK1 + nucleotide<br />
**[[4i5h]] – rMAPK1 (mutant) + inhibitor<br />
**[[3o71]] - rMAPK1 + colorectal cancer peptide<br />
**[[3zu7]], [[3zuv]] – rMAPK1 + ankyrin repeat protein<br />
**[[2y4i]] – raMAPK1+kinase suppressor of RAS 2 – rabbit<br />
**[[3oz6]] - MAPK1 - ''Cryptosporidium parvum''
 
*MAPK2
 
**[[1kwp]] – hMAPK2<br />
**[[3gok]] - hMAPK2 kinase domain<br />
**[[2pzy]], [[2p3g]], [[2jbo]], [[2jbp]] – hMAPK2 kinase domain +inhibitor<br />
**[[3a2c]], [[3kc3]], [[3fpm]], [[3fyj]], [[3fyk]], [[3r2b]], [[3r2y]], [[3r30]], [[3wi6]] - hMAPK2 kinase domain +inhibitor<br />
**[[3m2w]], [[3kga]], [[3ka0]], [[3m42]] – hMAPK2 kinase domain (mutant)+inhibitor<br />
**[[2oza]], [[2onl]] – hMAPK2+ hMAPK14<br />
**[[4tyh]] - hMAPK2+ hMAPK14 + inhibitor<br />
**[[1nxk]] – hMAPK2 + staurosporine<br />
**[[1ny3]] – hMAPK2 + ADP<br />
**[[2npt]] - hMAPK2 PHOX domain + hMAPK5<br />
**[[2erk]] – rMAPK2<br />
**[[3erk]], [[4erk]] – rMAPK2+inhibitor<br />
 
*MAPK3
 
**[[2zoq]] – hMAPK3<br />
**[[3r1n]], [[3she]], [[4qtb]] – hMAPK3 kinase domain +inhibitor<br />
 
*MAPK6
 
**[[3fxw]], [[3fhr]] – hMAPK3 kinase domain +inhibitor<br />
**[[2i6l]] – hMAPK6<br />
 
*MAPK7
**[[4ic8]] – hMAPK7<br />
**[[4b99]], [[4zsg]], [[4zsj]], [[4zsl]], [[5byy]], [[5byz]]  – hMAPK7+inhibitor<br />
**[[4ic7]] – hMAPK7+ MAP2K 5<br />
 
*MAPK8
 
**[[3o17]], [[2gmx]], [[2g01]], [[3vud]], [[3vug]], [[3vuh]], [[3vui]], [[3vuk]], [[3vul]], [[3vum]] – hMAPK8 (mutant)+JIP1 peptide<br />
**[[1ukh]], [[1uki]] - jMAPK8 JNK1+JIP1 peptide<br />
**[[3v3v]] - hMAPK8 JNK1+JIP1 peptide + quercedagetin<br />
**[[3o2m]] - hMAPK8 (mutant)+JIP1 peptide+biaryl tetrazole<br />
**[[2xrw]], [[2xs0]] - hMAPK8 + NFAT peptide<br />
**[[4ux9]] – hMAPK8 + MAPKK7 peptide<br />
**[[4yr8]] – hMAPK8 + MKP7 <br />
**[[3elj]], [[3pze]], [[4awi]], [[4l7f]], [[4qtd]] - hMAPK8+inhibitor<br />
**[[4e73]], [[4g1w]], [[4hys]], [[4hyu]], [[4izy]] – hMAPK8 + JIP1 +inhibitor<br />
**[[2no3]], [[2h96]] – hMAPK8 (mutant)+inhibitor<br />
 
*MAPK9
 
**[[3e7o]] - hMAPK9 (mutant)<br />
**[[3npc]] – hMAPK9 (mutant)+inhibitor<br />
 
*MAPK10
 
**[[3kvx]], [[3fv8]], [[2waj]], [[3fi2]], [[3fi3]], [[3da6]], [[2zdt]], [[2zdu]], [[3cgf]], [[3cgo]], [[2r9s]], [[2o0u]], [[2o2u]], [[2exc]], [[2b1p]], [[1pmn]], [[4z9l]], [[1pmu]], [[1pmv]], [[3oy1]], [[2ok1]], [[3ttj]], [[3tti]], [[3rtp]], [[3v6r]], [[3v6s]], [[4kkh]], [[4u79]], [[4whz]], [[4x21]], [[4y46]], [[4y5h]] – hMAPK10+inhibitor<br />
**[[3ptg]], [[4h39]] - hMAPK10 catalytic domain + JIP1 peptide <br />
**[[4h36]] – hMAPK10 catalytic domain + ATF2 peptide<br />
**[[4h3b]] – hMAPK10 catalytic domain + SAB peptide<br />
**[[4kke]], [[4kkg]] – hMAPK10 catalytic domain + AMPPNP<br />
**[[3g9l]], [[3g90]], [[3g9n]], [[2p33]] – hMAPK10 catalytic domain+inhibitor<br />
**[[3oxi]] - hMAPK10 + MAPK8 interacting protein + inhibitor<br />
 
*MAPK11
 
**[[3gp0]] – hMAPK11+inhibitor<br />
**[[3gc8]], [[3gc9]] – hMAPK11 (mutant)+inhibitor<br />
 
*MAPK13
 
**[[3coi]], [[4yno]], [[4myg]] – hMAPK13<br />
**[[4eyj]], [[4eym]], [[5ekn]], [[5eko]] - hMAPK13 +inhibitor<br />
 
*MAPK14
 
**[[3mgy]], [[3mh0]], [[3mh1]], [[3mh2]], [[3mh3]], [[3hvc]], [[3npq]], [[1wbo]], [[1r39]], [[2npq]], [[1wfc]], [[1cm8]], [[5etc]], [[5eti]], [[5uoj]] – hMAPK14<br />
**[[2lgc]] – hMAPK14 – NMR<br />
**[[3od6]], [[3ody]], [[3odz]], [[3oef]], [[3p4k]], [[2fsl]], [[2fsm]], [[2fso]], [[2fst]], [[1r3c]], [[4e5a]], [[4geo]] – hMAPK14 (mutant)<br />
**[[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]], [[4r3c]], [[4zth]], [[5lar]], [[5ml5]], [[5tbe]], [[5tco]] - hMAPK14+inhibitor<br />
**[[4e6a]], [[4e6c]], [[4e8a]] - hMAPK14+ lipid<br />
**[[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 />
**[[2y8o]] – hMAPK14 (mutant) + dual specificity MAP2K peptide<br />
**[[4ka3]], [[4loo]], [[4lop]], [[4loq]] – hMAPK14 + docking peptide<br />
**[[5eta]] – hMAPK14 + peptide<br />
**[[3tg1]] – hMAPK14 + MAPK phosphatase 5<br />
**[[5etf]] – hMAPK14 + MAPKK 6<br />
**[[2gtn]], [[2gtm]], [[3p5k]], [[3p78]], [[3p79]], [[3p7a]], [[3p7b]], [[3p7c]] - mMAPK14+inhibitor<br />
**[[2ghm]], [[2ghl]], [[1ywr]] - mMAPK14 (mutant)+inhibitor<br />
**[[3py3]] - mMAPK14 phosphorylated<br />
**[[1yw2]], [[1p38]] - mMAPK14 (mutant)<br />
**[[1lew]] - mMAPK14+MEF2A<br />
**[[1lez]] - mMAPK14+MKK3B<br />
 
*MAPK Fus3
 
**[[2f9g]], [[2b9f]] – yMAPK Fus3 – yeast<br />
**[[2fa2]] – yMAPK Fus3 (mutant)<br />
**[[2f49]] - yMAPK Fus3 +STE5 peptide<br />
**[[2b9h]], [[2b9i]] - yMAPK Fus3 (mutant)+MSG5 peptide<br />
**[[2b9j]] - yMAPK Fus3 (mutant)+FAR1 peptide<br />
 
*MAPK


**[[3rp9]] – MAPK – ''Toxoplasma gondii''<br />
**[[3uib]] – MAPK + inhibitor – ''Leishmania major''<br />
}}
== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 11:23, 20 January 2022

Function

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, MAP2K and MAP3K which are activated by phosphorylation[1].

See also Mitogen-activated protein kinase cascade.

  • MAPK1 or ERK2 and MAPK3 are activated in response to growth factors. For MAPK1 representations see Michael Roberts/BIOL115/ERK2.
  • MAPK6 is activated by phorbol esters.
  • MAPK7 is activated by stress stimuli.
  • 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.
  • 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 p38 MAPK (UMass Chem 423 Student Projects 2011-2).

Relevance

MAPK cascade is elevated in cancer cells, hence MAPK inhibitors are tested as potential cancer therapy.

Disease

MAPK14 is associated with acquired hyperkeratosis and prostate transitional cell carcinoma.

Structural highlights

[2]. Water molecule are shown as red sphere.

3D Structures of Mitogen-activated protein kinase

Mitogen-activated protein kinase 3D structures


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

Drag the structure with the mouse to rotate

ReferencesReferences

  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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Alexander Berchansky, Michal Harel, Joel L. Sussman
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