Mitogen-activated protein kinase: Difference between revisions

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New page: left|thumb|300px|Crystal Structure of the Mitogen-activated protein kinase, [[1erk]] {{STRUCTURE_1erk| right| PDB=1erk | SCENE= |CAPTION=Mitogen-activated protein kina...
 
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[[Image:1erk.png|left|thumb|300px|Crystal Structure of the Mitogen-activated protein kinase, [[1erk]]]]
<StructureSection load='' size='350' side='right' caption='Human MAPK1 complex with inhibitor and sulfate (PDB entry [[2ojg]])' scene='43/438476/Cv/2'>
{{STRUCTURE_1erk| right| PDB=1erk  |  SCENE= |CAPTION=Mitogen-activated protein kinase, [[1erk]] }}
== 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, MAP2K and 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, MAPK11, MAPK12, MAPK13, MAPK14 are stress-activated. The images on the left and right  correspond to one representative MAPK structure, ''i.e.'' the rat MAPK1 ([[1erk]]).
See also [[Mitogen-activated protein kinase cascade]].


{{TOC limit|limit=2}}
* '''MAPK1''' or '''ERK2''' and '''MAPK3''' are activated in response to growth factors.  For '''MAPK1''' representations see [[Michael Roberts/BIOL115/ERK2]].<br />
<br />
*  '''MAPK6''' is activated by phorbol esters.<br />
<br />
* '''MAPK7''' is activated by stress stimuli.<br />
<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 />
<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 [[UMass Chem 423 Student Projects 2011-2#p38 kinase|p38 MAPK (UMass Chem 423 Student Projects 2011-2)]].
<br />


== 3D Structures of Mitogen-activated protein kinase ==
== Relevance ==
MAPK cascade is elevated in cancer cells, hence MAPK inhibitors are tested as potential cancer therapy.


===MAPK1===
== Disease ==
[[3i5z]], [[3i60]], [[2e14]], [[2ojg]], [[2oji]], [[2ojj]], [[2ok1]], [[1wzy]], [[1tvo]] – hMAPK1+inhibitor - human<br />
MAPK14 is associated with acquired hyperkeratosis and prostate transitional cell carcinoma.
[[2z7l]], [[3c9w]] - rMAPK1+inhibitor – rat<br />
[[1erk]] - rMAPK1<br />
[[1gol]] - rMAPK1 (mutant)<br />
[[2gph]] - rMAPK1 (mutant)+HEPTP (mutant)<br />
[[2fys]] - rMAPK1 + KIM peptide<br />
[[2y4i]] – raMAPK1+kinase suppressor of RAS 2 – rabbit<br />


===MAPK2===
== Structural highlights ==
<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.


[[3gok]] - hMAPK2 kinase domain<br />
== 3D Structures of Mitogen-activated protein kinase ==
[[2pzy]], [[2p3g]], [[2jbo]], [[2jbp]] – hMAPK2+inhibitor<br />
[[Mitogen-activated protein kinase 3D structures]]
[[3a2c]], [[3kc3]], [[3fpm]], [[3fyj]], [[3fyk]] - hMAPK2 kinase domain +inhibitor<br />
[[3m2w]], [[3kga]], [[3ka0]] – hMAPK2 kinase domain (mutant)+inhibitor<br />
[[2oza]], [[2okr]], [[2onl]] – hMAPK2+ hMAPK14<br />
[[2npt]] - hMAPK2+ hMAPK5<br />
[[2erk]] – rMAPK2<br />
[[3erk]], [[4erk]] – rMAPK2+inhibitor<br />
 
===MAPK3===
[[2zoq]] – hMAPK3<br />
 
===MAPK6===
 
[[3fxw]], [[3fhr]] – hMAPK3 kinase domain +inhibitor<br />
[[2i6l]] – hMAPK6<br />
 
===MAPK8===
 
[[3o17]], [[2gmx]], [[2g01]] – hMAPK8 (mutant)+JIP1 peptide<br />
[[3o2m]] - hMAPK8 (mutant)+JIP1 peptide+biaryl tetrazole<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]], [[1pmq]], [[1pmu]], [[1pmv]] – hMAPK10+inhibitor<br />
[[3g9l]], [[3g90]], [[3g9n]], [[2p33]] – hMAPK10 kinase domain+inhibitor<br />
 
===MAPK11===
 
[[3gp0]] – hMAPK11+inhibitor<br />
[[3gc8]], [[3gc9]] – hMAPK11 (mutant)+inhibitor<br />
 
===MAPK13===
[[3coi]] – hMAPK13<br />
 
===MAPK14===
 
[[3mgy]], [[3mh0]], [[3mh1]], [[3mh2]], [[3mh3]], [[3hvc]], [[3npq]], [[1wbo]], [[1r39]] – hMAPK14<br />
[[3od6]], [[3ody]], [[3odz]], [[3oef]], [[3p4k]], [[2fsl]], [[2fsm]], [[2fso]], [[2fst]], [[1r3c]] – 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]] - hMAPK14+inhibitor<br />
[[3o8t]], [[3mpa]], [[3obg]], [[3o8u]], [[3o8p]], [[3obj]], [[3oc1]], [[3hub]], [[3l8s]], [[3hv3]], [[3iw5]], [[3iw6]], [[3iw7]], [[3iw8]], [[3k3j]], [[3gc7]], [[3gcp]], [[3gcq]], [[3gcs]], [[3gcv]], [[3ds6]], [[2i0h]], [[1ove]] - hMAPK14 (mutant)+inhibitor<br />
[[2gtn]], [[2gtm]] - mMAPK14+inhibitor<br />
[[2ghm]], [[2ghl]], [[1ywr]] - mMAPK14 (mutant)+inhibitor<br />
[[1yw2]] - mMAPK14 (mutant)<br />
[[1lew]] - mMAPK14+MEF2A<br />
[[1lez]] - mMAPK14+MKK3B<br />
 
===MAPK p38===
 
[[1wfc]] - hMAPK p38<br />
[[1bl6]], [[1bl7]], [[1bmk]], [[1a9u]], [[1ian]] – hMAPK p38 (mutant)+inhibitor<br />
[[1p38]] - mMAPK p38 (mutant) - mouse<br />
 
===MAPK FUSS===


[[2f9g]], [[2b9f]] – yMAPK FUSS – yeast<br />
</StructureSection>
[[2fa2]] – yMAPK FUSS (mutant)<br />
[[2f49]] - yMAPK FUSS+STE5 peptide<br />
[[2b9h]] - yMAPK FUSS (mutant)+MSG5 peptide<br />
[[2b9j]] - yMAPK FUSS (mutant)+FAR1 peptide<br />


== 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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