ERK*

Protein ERK*

Identifiers
HUGO:MAPK1 HUGO:MAPK2 HUGO:MAPK3 HUGO:MAPK4
mitogen-activated protein kinase 3
HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361
mitogen-activated protein kinase 1
HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482
mitogen-activated protein kinase 6
HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659
PRKM1 PRKM2
PRKM3
HUGO:MAPK1 HGNC:6871 ENTREZ:5594 UNIPROT:P28482 GENECARDS:MAPK1 REACTOME:59283 KEGG:5594 ATLASONC:MAPK1ID41288ch22q11 WIKI:MAPK1
HUGO:MAPK3 HGNC:6877 ENTREZ:5595 UNIPROT:P27361 GENECARDS:MAPK3 KEGG:5595 ATLASONC:MAPK3ID425ch16p11 WIKI:MAPK3
mitogen-activated protein kinase 4
HUGO:MAPK4 HGNC:6878 ENTREZ:5596 UNIPROT:P31152 GENECARDS:MAPK4 KEGG:5596 ATLASONC:MAPK4ID41293ch18q21 WIKI:MAPK4
HUGO:MAPK6 HGNC:6879 ENTREZ:5597 UNIPROT:Q16659 GENECARDS:MAPK6 KEGG:5597 ATLASONC:MAPK6ID43349ch15q21 WIKI:MAPK6
ERK, ERK2, MAPK2, p41mapk

Maps_Modules
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / CASPASES
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / NECROPTOSIS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK
Survival / WNT_NON_CANONICAL

References
Phosphorylated ERK negatively regulates KSR1/B-Raf interaction downregulating signal transmission.
In restig cells ERK1/2 are localised in the cytoplasm due to binding to many cytoplasmic anchors or scaffold proteins.
MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes)
PMID:19541618 PMID:19565474 PMID:15547943

ERK*@Cytosol

References
mo_re126:( motility ) PMID:23989302 PMID:19152186 PMID:27452906

ERK*|pho@Cytosol

References
mo_re126:( motility ) PMID:23989302 PMID:19152186 PMID:27452906

ERK*|pho@Nucleus

References
mo_re127:( motility ) PMID:23989302 PMID:19152186

ERK*@Cytoplasm

References
su_mpk1_mpk1_re187( Survival ):
JNK pathway negatively regulates ERK pathway by uncoupling ERK activation from MEK via activation of JUN transcriptional activity.
A direct interaction between P38 and ERK has been proposed as a mechanism to inhibit ERK phosphorylation. AP-1 mediated gene expression inhibits ERK phosphorylation.
PMID:12738796 PMID:18039929
su_mpk1_mpk1_re189( Survival ):
MEK is continuously dephosphorylated by PP2A (PPP2CA) whose activity is stimulated by P38: P38 activity increases the physical association between PP2A and MEK/ERK complex. A direct interaction between P38 and ERK has been proposed as a mechanism to inhibit ERK phosphorylation. AP-1 mediated gene expression inhibits ERK phosphorylation.
PMID:18039929
su_mpk1_mpk1_re16( Survival ):
ERK recruitment is enhanced by KSR1. ERK is then phosphorylated by MEK.
PMID:19541618
su_mpk1_mpk1_re22( Survival ):
Recruitment and phosphorylation of ERK1 on late endosomes.
PMID:17496910
su_mpk1_mpk1_re57( Survival ):
Sef1 which is a putative transmembrane protein of the Golgi apparatus seems to be a scaffold protein that recruits ERK1/2 and MEK1/2 to its vicinity and probably allows their activation by Golgi-localised Ras proteins.
PMID:19565474
su_mpk1_mpk1_re62( Survival ):
The component kinases of the ERK cascade Raf-1 MEK and ERK assemble using beta-ARRESTIN as a scaffold and leading to activation of ERK. Endocytosis of these receptor/beta-ARRESTIN complexes by clathrin-coated pits results in the targeting of activated ERK to endosomal vesicles.
The beta-ARRESTIN occupied receptor undergoes internalisation into early endosomes. At the early endosome stage beta-ARRESTIN recruits both MEK1/2 and ERK1/2 and is likely to facilitate their activation upon GPCR stimulation.
PMID:11226259 PMID:19565474
su_mpk1_mpk1_re159:( Survival ) Any other mechanism of ERK activation not explicitly modelled.
su_wnc1_s_wnc2_re62:( Survival ) PMID:21965663, PMID:12063245

ERK*|pho|pho@Nucleus

References
su_mpk1_mpk1_re65( Survival ):
Mxi2 is a splicing isoform of P38. It directly interacts with ERK1/2. Mxi2 prolongs ERK activation (in the nucleus) by binding.
Mxi2 could suffice to promote the transport of ERK1/2 to the nucleus in the absence of further stimulation.
PMID:12697810 PMID:17255949
su_mpk1_mpk1_re91( Survival ):
The rapid and efficient phosphorylation of Elk1 by ERKs is enabled by a direct interaction between the two proteins.
ELK1 is a nuclear P38 target.
ELK1 is a nuclear JNK target.
PMID:16393692 PMID:20506250 PMID:11274345
su_mpk1_mpk1_re93( Survival ):
DUSP5 represents an inducible ERK-specific MKP and it functions as both a nuclear anchor and inactivator of ERK MODULE:MAPK in mammalian cells.
PMID:17052211
su_mpk1_mpk1_re95( Survival ):
MSK1 and MSK2 are potently activated (by phosphorylation) in vivo by ERK1/2 and P38 but not JNK. They are localised in the nucleus of quiescent and activated cells which suggest that they may preferentially phosphorylate nuclear substrates.
PMID:15187187
su_mpk1_mpk1_re177( Survival ):
Phosphorylation by both ERKs and their downstream RSKs can stabilise the c-FOS protein for several hours. The combination of these phosphorylations allows c-FOS sustained activity.
PMID:16393692

ERK*|pho|pho@Mitochondria

References
su_mpk1_mpk1_re119( Survival ):
A small fraction of both ERK and GSK3 is constitutively found in a protease-protected mitochondrial compartment. How this fraction of ERK and GSK3 enters mitochondria is an open question.
PMID:20080742
su_mpk1_mpk1_re114( Survival ):
We postulate a model in which ERK activation inhibits GSK3 activity (by phosphorylation) its association to CYPD and CYPD phosphorylation (by GSK3) leading to PTP desensitisation.

ERK*|pho|pho@Cytoplasm

References
su_mpk1_mpk1_re29( Survival ):
Docking of activated ERK to the KSR1 scaffold negatively regulates the interaction between KSR1 and B-Raf.
PMID:19541618
su_mpk1_mpk1_re36( Survival ):
Activation of ERK pathway caused the dissociation of the MP1/ERK1 complex.
MP1 constitutively binds MEK1 but releases ERK / MAPK after activation. This turnover could provide an amplification mechanism that translates low MEK activity into sustained ERK / MAPK activation in which MP1 continues to supply MEK1 with inactive ERK / MAPK for phosphorylation.
PMID:15547943 PMID:16227978
su_mpk1_mpk1_re159:( Survival ) Any other mechanism of ERK activation not explicitly modelled.
su_mpk1_mpk1_re32( Survival ):
Caspase9 is phosphorylated on Thr125 in a MEK1/2-dependent manner in vivo. Furthermore caspase9 is efficiently phosphorylated on Thr125 by ERK in vitro suggesting that it is targeted directly by ERK in vivo. This is one of the ways ERK plays its anti-apoptotic role.
PMID:12792650
su_mpk1_mpk1_re65( Survival ):
Mxi2 is a splicing isoform of P38. It directly interacts with ERK1/2. Mxi2 prolongs ERK activation (in the nucleus) by binding.
Mxi2 could suffice to promote the transport of ERK1/2 to the nucleus in the absence of further stimulation.
PMID:12697810 PMID:17255949
su_mpk1_mpk1_re83( Survival ):
Upon activation scaffold proteins serve as platforms in which ERK dimers are assembled forming complexes capable of interacting with and activating cognate cytoplasmic substrates.
PMID:18775330
su_mpk1_mpk1_re84( Survival ):
Unlike many other scaffolds ERK1/2 do not dissociate from Sef1 upon stimulation and therefore nuclear translocation of the Sef1 anchored fraction of ERK1/2 molecules is blocked.
PMID:18775330 PMID:19565474
su_mpk1_mpk1_re87( Survival ):
Beta-ARRESTIN prevents the translocation of ERK into the nucleus thereby reducing phosphorylation of nuclear substrates and consequently MODULE:MAPK -dependent gene expression.
PMID:18775330 PMID:19091303
su_mpk1_mpk1_re90( Survival ):
DUSP6 may capture activated ERK2 dephosphorylate it and anchor the inactive kinase in the cytoplasm.
PMID:17052211
su_mpk1_mpk1_re109( Survival ):
ERK phosphorylates GSK3B to facilitate phosphorylation of GSK3B by p90RSK (RSK) which leads to the inactivation of GSK3B. GSK3B docking to ERK and phosphorylation by ERK are required for inhibition of beta-catenin (CTNNB1) ubiquitination and therefore for its stabilisation. ERK GSK3B and p90RSK (RSK) are in the same complex.
PMID:16039586
su_mpk1_mpk1_re119( Survival ):
A small fraction of both ERK and GSK3 is constitutively found in a protease-protected mitochondrial compartment. How this fraction of ERK and GSK3 enters mitochondria is an open question.
PMID:20080742
su_mpk1_mpk1_re165( Survival ):
MNKs are cytoplasmic targets of ERK and P38.
PMID:15187187
su_mpk1_mpk1_re187( Survival ):
JNK pathway negatively regulates ERK pathway by uncoupling ERK activation from MEK via activation of JUN transcriptional activity.
A direct interaction between P38 and ERK has been proposed as a mechanism to inhibit ERK phosphorylation. AP-1 mediated gene expression inhibits ERK phosphorylation.
PMID:12738796 PMID:18039929
su_mpk1_mpk1_re264( Survival ):
PDK1 is a PI3K target leading to activation of P70 (through phosphorylation) and subsequent cell growth.
P70 activation requires both ERK cascade and PI3K/AKT cascade at least in some cell types.
PMID:12040186 PMID:11940578 PMID:10601235 PMID:11431469
su_mpk1_mpk1_re275( Survival ):
Sprouty is induced by activated ERK through phosphorylation on Tyr55. It positively regulates EGFR signalling by sequestering Cbl whereas it negatively regulates FGFR signalling by sequestering Grb2 from FSR2.
PMID:15173823