MAPK targets/ Nuclear events mediated by MAP kinases (Homo sapiens)

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1-34894541010, 11612, 13714, 15nucleoplasmCyclic-AMP-dependent transcription factor ATF-1ATPActivated Protein 1 (AP-1) heterodimer cJUN/ATF2Phosphorylated JNKs: MAPK8, MAPK9, MAPK10Phospho-MSK1Ribosomal protein S6 kinaseATPADPMSK1Activated Protein 1 (AP-1) heterodimer cJUN/cFOSc-FOSADPPP2A-ABdeltaC complexPhospho-MAP kinase-activated protein kinase 2Phospho-MEF2Phospho-ERK1/2/5ADPERK1/2/5ERK-specific DUSPATPc-JunPhospho-Cyclic-AMP-dependent transcription factor ATF-1Phospho-ERK dimerPhospho-MAP kinase p38 alpha/betaphospho-CREBADPMEF2ATF-2ADPPhospho-ERK5Phospho-ELK1ADPCREBATF-2-PActivated MAPK kinases ERK1/2, JNK, p38ATPc-FOS -PPhospho-Ribosomal protein S6 kinasec-Jun-POrthophosphateELK1ATPATPH2O


Description

MAPKs are protein kinases that, once activated, phosphorylate their specific cytosolic or nuclear substrates at serine and/or threonine residues. Such phosphorylation events can either positively or negatively regulate substrate, and thus entire signaling cascade activity.

The major cytosolic target of activated ERKs are RSKs (90 kDa Ribosomal protein S6 Kinase). Active RSKs translocates to the nucleus and phosphorylates such factors as c-Fos(on Ser362), SRF (Serum Response Factor) at Ser103, and CREB (Cyclic AMP Response Element-Binding protein) at Ser133. In the nucleus activated ERKs phosphorylate many other targets such as MSKs (Mitogen- and Stress-activated protein kinases), MNK (MAP interacting kinase) and Elk1 (on Serine383 and Serine389). ERK can directly phosphorylate CREB and also AP-1 components c-Jun and c-Fos. Another important target of ERK is NF-KappaB. Recent studies reveals that nuclear pore proteins are direct substrates for ERK (Kosako H et al, 2009). Other ERK nuclear targets include c-Myc, HSF1 (Heat-Shock Factor-1), STAT1/3 (Signal Transducer and Activator of Transcription-1/3), and many more transcription factors.

Activated p38 MAPK is able to phosphorylate a variety of substrates, including transcription factors STAT1, p53, ATF2 (Activating transcription factor 2), MEF2 (Myocyte enhancer factor-2), protein kinases MSK1, MNK, MAPKAPK2/3, death/survival molecules (Bcl2, caspases), and cell cycle control factors (cyclin D1).

JNK, once activated, phosphorylates a range of nuclear substrates, including transcription factors Jun, ATF, Elk1, p53, STAT1/3 and many other factors. JNK has also been shown to directly phosphorylate many nuclear hormone receptors. For example, peroxisome proliferator-activated receptor 1 (PPAR-1) and retinoic acid receptors RXR and RAR are substrates for JNK. Other JNK targets are heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Other adaptor and scaffold proteins have also been characterized as nonnuclear substrates of JNK.</div>

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History

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CompareRevisionActionTimeUserComment
114815view16:31, 25 January 2021ReactomeTeamReactome version 75
113260view11:32, 2 November 2020ReactomeTeamReactome version 74
112475view15:42, 9 October 2020ReactomeTeamReactome version 73
101386view11:27, 1 November 2018ReactomeTeamreactome version 66
100924view21:03, 31 October 2018ReactomeTeamreactome version 65
100464view19:37, 31 October 2018ReactomeTeamreactome version 64
100010view16:21, 31 October 2018ReactomeTeamreactome version 63
99563view14:54, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93906view13:44, 16 August 2017ReactomeTeamreactome version 61
93480view11:24, 9 August 2017ReactomeTeamreactome version 61
86577view09:21, 11 July 2016ReactomeTeamreactome version 56
83294view10:40, 18 November 2015ReactomeTeamVersion54
81428view12:57, 21 August 2015ReactomeTeamVersion53
76899view08:17, 17 July 2014ReactomeTeamFixed remaining interactions
76604view11:58, 16 July 2014ReactomeTeamFixed remaining interactions
75935view09:59, 11 June 2014ReactomeTeamRe-fixing comment source
75637view10:52, 10 June 2014ReactomeTeamReactome 48 Update
74992view13:51, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74636view08:41, 30 April 2014ReactomeTeamReactome46
44891view10:15, 6 October 2011MartijnVanIerselOntology Term : 'MAPK signaling pathway' added !
42063view21:54, 4 March 2011MaintBotAutomatic update
39871view05:54, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ADP Metabolite16761 (ChEBI)
ATF-2 ProteinP15336 (UniProt)
ATF-2-P ProteinP15336 (UniProt)
ATP Metabolite15422 (ChEBI)
Activated MAPK

kinases ERK1/2, JNK, p38

UnknownREACT_21930 (Reactome)
Activated Protein 1

(AP-1) heterodimer cJUN/ATF2

ComplexREACT_21429 (Reactome)
Activated Protein 1 (AP-1)

heterodimer cJUN/cFOS

ComplexREACT_21707 (Reactome)
CREB ProteinP16220 (UniProt)
Cyclic-AMP-

dependent transcription factor ATF-1

ProteinP18846 (UniProt)
ELK1 ProteinREACT_13391 (Reactome)
ERK-specific DUSP UnknownREACT_12976 (Reactome)
ERK1/2/5 ProteinREACT_13316 (Reactome)
H2O Metabolite15377 (ChEBI)
MEF2 ProteinREACT_13049 (Reactome)
MSK1 ProteinO75582 (UniProt)
Orthophosphate Metabolite18367 (ChEBI)
PP2A-ABdeltaC

complex

ComplexREACT_2369 (Reactome)
Phospho-

ELK1

ProteinREACT_13225 (Reactome)
Phospho-

ERK1/2/5

ProteinREACT_13301 (Reactome)
Phospho-

Ribosomal protein S6 kinase

ProteinREACT_12696 (Reactome)
Phospho-Cyclic-

AMP-dependent transcription factor ATF-1

ProteinP18846 (UniProt)
Phospho-ERK

dimer

UnknownREACT_12827 (Reactome)
Phospho-ERK5 ProteinQ13164 (UniProt)
Phospho-MAP

kinase-activated protein kinase 2

ProteinP49137 (UniProt)
Phospho-MAP kinase

p38 alpha/beta

ProteinREACT_12925 (Reactome)
Phospho-MEF2 ProteinREACT_12996 (Reactome)
Phospho-MSK1 ProteinO75582 (UniProt)
Phosphorylated JNKs:

MAPK8, MAPK9, MAPK10

ProteinREACT_22035 (Reactome)
Ribosomal protein S6

kinase

ProteinREACT_13229 (Reactome)
c-FOS ProteinP01100 (UniProt)
c-FOS -P ProteinP01100 (UniProt)
c-Jun ProteinP05412 (UniProt)
c-Jun-P ProteinP05412 (UniProt)
phospho-CREB ProteinP16220 (UniProt)

Annotated Interactions

No annotated interactions

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