ERK*

Protein ERK* map

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

Maps_Modules
 Apoptosis  map  / AKT_MTOR  map
 Apoptosis  map  / CASPASES  map
 Apoptosis  map  / MOMP_REGULATION  map
 Survival  map  / MAPK  map
 Survival  map  / WNT_NON_CANONICAL  map

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*@Cytoplasm

References
a_re498( Apoptosis  map ):
PMID:12792650
Direct phosphorylation of CASP9 by ERK2 sufficient to block CASP9 processing
in vitro, recombinant hCASP9 phosphorylated on T125 by cytosolic extract or ERK2
in Hela cells, interaction GST-CASP9 / ERK
in Hela or HEK293, CASP9 T125 phosphorylation by OA, consititutively active MEK1, EGF or TPA
PMID:17466630
CASP9 T125 phosphorylation by CCNB1:CDC2
comment: phosphorylation during mitosis, when nuclear envelope is broken down
PMID:19081073
CASP9 T125 phosphorylation by DYRK1A
PMID:19016842
PMID:19586613
CASP9 T125 phosphorylation by DYRK1A and p38

ERK*|​pho|​pho@Nucleus

References
s_mpk1_re65( Survival  map ):
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
s_mpk1_re91( Survival  map ):
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
s_mpk1_re93( Survival  map ):
DUSP5 represents an inducible ERK-specific MKP and it functions as both a nuclear anchor and inactivator of ERK MODULE:MAPK map in mammalian cells.
PMID:17052211
s_mpk1_re95( Survival  map ):
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
s_mpk1_re177( Survival  map ):
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
s_mpk1_re119( Survival  map ):
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
s_mpk1_re114( Survival  map ):
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.
s_s_mpk1_re114( Survival  map ):

ERK*|​pho|​pho@Cytoplasm

References
s_mpk1_re29( Survival  map ):
Docking of activated ERK to the KSR1 scaffold negatively regulates the interaction between KSR1 and B-Raf.
PMID:19541618
s_mpk1_re36( Survival  map ):
Activation of ERK pathway caused the dissociation of the MP1/ERK1 complex.
MP1 constitutively binds MEK1 but releases ERK / MAPK  map after activation. This turnover could provide an amplification mechanism that translates low MEK activity into sustained ERK / MAPK  map activation in which MP1 continues to supply MEK1 with inactive ERK / MAPK  map for phosphorylation.
PMID:15547943 PMID:16227978
s_mpk1_re159:( Survival  map ) Any other mechanism of ERK activation not explicitly modelled.
s_mpk1_re32( Survival  map ):
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
s_mpk1_re65( Survival  map ):
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
s_mpk1_re83( Survival  map ):
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
s_mpk1_re84( Survival  map ):
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
s_mpk1_re87( Survival  map ):
Beta-ARRESTIN prevents the translocation of ERK into the nucleus thereby reducing phosphorylation of nuclear substrates and consequently MODULE:MAPK map -dependent gene expression.
PMID:18775330 PMID:19091303
s_mpk1_re90( Survival  map ):
DUSP6 may capture activated ERK2 dephosphorylate it and anchor the inactive kinase in the cytoplasm.
PMID:17052211
s_mpk1_re109( Survival  map ):
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
s_mpk1_re119( Survival  map ):
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
s_mpk1_re165( Survival  map ):
MNKs are cytoplasmic targets of ERK and P38.
PMID:15187187
s_mpk1_re187( Survival  map ):
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
s_mpk1_re264( Survival  map ):
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
s_mpk1_re275( Survival  map ):
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
s_s_mpk1_re84( Survival  map ):
s_s_mpk1_re87( Survival  map ):


Modifications:
In compartment: Cytoplasm
  1. ERK*@Cytoplasm map

  2. ERK*|​pho|​pho@Cytoplasm map

In compartment: Mitochondria

  1. ERK*|​pho|​pho@Mitochondria map

In compartment: Nucleus

  1. ERK*|​pho|​pho@Nucleus map

Participates in complexes:
In compartment: Cytoplasm

  1. DUSP6:​ERK*@Cytoplasm map

  2. ERK*|​pho|​pho:​KSR1:​MEK*|​pho|​pho@Cytoplasm map
  3. ERK*|​pho|​pho:​MEK*|​pho|​pho:​SEF*@Cytoplasm map
  4. ERK*|​pho|​pho:​GSK3_beta_*|​pho:​RSK*|​pho@Cytoplasm map
  5. ERK*|​pho|​pho|​hm2:​KSR1:​MEK*|​pho|​pho@Cytoplasm map
  6. ERK*|​pho|​pho|​hm2:​MEK*|​pho|​pho:​SEF*@Cytoplasm map
  7. ERK*|​pho|​pho|​hm2:​MEK*|​pho|​pho:​_beta_-Arrestin2*@Cytoplasm map

In compartment: Early Endosomes

  1. ERK*|​pho|​pho:​MEK*|​pho|​pho:​_beta_-Arrestin2*@Early Endosomes map

  2. ERK*|​pho|​pho:​GPCR*:​GRK*:​MEK*|​pho|​pho:​RAF1|​pho:​_beta_-Arrestin2*@Early Endosomes map

In compartment: Golgi Apparatus

  1. ERK*:​MEK*:​SEF*@Golgi Apparatus map

In compartment: Late Endosomes

  1. ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map

In compartment: Nucleus

  1. DUSP5:​ERK*@Nucleus map

In compartment: Plasma Membrane

  1. BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map

Participates in reactions:
As Reactant or Product:

  1. ERK*|​pho|​pho@Cytoplasm map + GSK3_beta_*@Cytoplasm map + RSK*|​pho@Cytoplasm map map ERK*|​pho|​pho:​GSK3_beta_*|​pho:​RSK*|​pho@Cytoplasm map

  2. ERK*|​pho|​pho@Cytoplasm map map ERK*|​pho|​pho@Mitochondria map
  3. ERK*@Cytoplasm map map ERK*|​pho|​pho@Cytoplasm map
  4. BRAF|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + ERK*@Cytoplasm map map BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  5. ERK*|​pho|​pho@Cytoplasm map map ERK*@Cytoplasm map
  6. ERK*|​pho|​pho:​KSR1:​MEK*|​pho|​pho@Cytoplasm map map KSR1:​MEK*@Cytoplasm map + ERK*@Cytoplasm map
  7. ERK*|​pho|​pho:​MEK*|​pho|​pho:​SEF*@Cytoplasm map map MEK*:​SEF*@Cytoplasm map + ERK*@Cytoplasm map
  8. ERK*|​pho|​pho:​MEK*|​pho|​pho:​_beta_-Arrestin2*@Early Endosomes map map MEK*:​_beta_-Arrestin2*@Cytoplasm map + ERK*@Cytoplasm map
  9. ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map map GRB2:​LAMTOR2:​MEK*:​MP1*:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map + ERK*@Cytoplasm map + RAF1@Cytoplasm map
  10. ERK*@Cytoplasm map + GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map map ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map
  11. BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map map KSR1:​MEK*@Cytoplasm map + BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map + ERK*|​pho|​pho@Cytoplasm map
  12. ERK*|​pho|​pho:​GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map map GRB2:​LAMTOR2:​MEK*|​pho|​pho:​MP1*:​RAF1|​pho:​RAS*|​pho:​RTK*:​SOS*@Late Endosomes map + ERK*|​pho|​pho@Cytoplasm map
  13. MEK*@Cytoplasm map + ERK*@Cytoplasm map + SEF*@Golgi Apparatus map map ERK*:​MEK*:​SEF*@Golgi Apparatus map
  14. ERK*:​MEK*:​SEF*@Golgi Apparatus map map ERK*|​pho|​pho:​MEK*|​pho|​pho:​SEF*@Cytoplasm map
  15. GPCR*|​pho:​GRK*:​_beta_-Arrestin2*@Plasma Membrane map + ERK*@Cytoplasm map + RAF1@Cytoplasm map + MEK*@Cytoplasm map map ERK*|​pho|​pho:​GPCR*:​GRK*:​MEK*|​pho|​pho:​RAF1|​pho:​_beta_-Arrestin2*@Early Endosomes map
  16. ERK*|​pho|​pho@Cytoplasm map map ERK*|​pho|​pho@Nucleus map
  17. BRAF|​pho:​ERK*|​pho|​pho:​GRB2:​KSR1:​MEK*|​pho|​pho:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map map ERK*|​pho|​pho:​KSR1:​MEK*|​pho|​pho@Cytoplasm map + BRAF|​pho:​GRB2:​RAS*|​pho:​RTK*:​SOS*@Plasma Membrane map
  18. ERK*|​pho|​pho:​KSR1:​MEK*|​pho|​pho@Cytoplasm map + ERK*|​pho|​pho@Cytoplasm map map ERK*|​pho|​pho|​hm2:​KSR1:​MEK*|​pho|​pho@Cytoplasm map
  19. ERK*|​pho|​pho:​MEK*|​pho|​pho:​SEF*@Cytoplasm map + ERK*|​pho|​pho@Cytoplasm map map ERK*|​pho|​pho|​hm2:​MEK*|​pho|​pho:​SEF*@Cytoplasm map
  20. ERK*|​pho|​pho:​GPCR*:​GRK*:​MEK*|​pho|​pho:​RAF1|​pho:​_beta_-Arrestin2*@Early Endosomes map map GPCR*:​GRK*@Early Endosomes map + ERK*|​pho|​pho:​MEK*|​pho|​pho:​_beta_-Arrestin2*@Early Endosomes map + RAF1@Cytoplasm map
  21. ERK*|​pho|​pho:​MEK*|​pho|​pho:​_beta_-Arrestin2*@Early Endosomes map + ERK*|​pho|​pho@Cytoplasm map map ERK*|​pho|​pho|​hm2:​MEK*|​pho|​pho:​_beta_-Arrestin2*@Cytoplasm map
  22. ERK*|​pho|​pho@Cytoplasm map + DUSP6@Cytoplasm map map DUSP6:​ERK*@Cytoplasm map
  23. ERK*|​pho|​pho@Nucleus map + DUSP5@Nucleus map map DUSP5:​ERK*@Nucleus map
  24. MAPK pathway@Cytoplasm map map ERK*@Cytoplasm map
  25. FGF2:​RTK*@Cytoplasm map map ERK*@Cytoplasm map

As Catalyser:

  1. BCL2@Mitochondrial outer membrane map map BCL2|​pho@Mitochondrial outer membrane map

  2. TSC1:​TSC2|​M1_unk@Cytoplasm map map TSC1@Cytoplasm map + TSC2|​S664_pho|​M1_unk@Cytoplasm map
  3. MLST8:​MTOR:​RPTOR@Cytoplasm map map MLST8:​MTOR:​RPTOR|​pho@Cytoplasm map
  4. BimEL*@Cytoplasm map map BimEL*|​S69_pho@Cytoplasm map
  5. Caspase9*|​S196_unk|​S144_unk|​Y153_unk@Cytoplasm map map Caspase9*|​S196_unk|​T125_pho|​S144_unk|​Y153_unk@Cytoplasm map
  6. GSK3_beta_*@Mitochondria map map GSK3_beta_*|​pho@Mitochondria map
  7. MNK*@Cytoplasm map map MNK*|​pho@Cytoplasm map
  8. FOS@Nucleus map map FOS|​pho@Nucleus map
  9. p70_alpha_*@Cytoplasm map map p70_alpha_*|​pho@Cytoplasm map
  10. SPRY2@Cytoplasm map map SPRY2|​pho@Cytoplasm map
  11. SPRY1@Cytoplasm map map SPRY1|​pho@Cytoplasm map
  12. Caspase9*@Cytoplasm map map Caspase9*|​pho@Cytoplasm map
  13. PLA2G4A@Cytoplasm map map PLA2G4A|​pho@Cytoplasm map
  14. ELK1@Nucleus map map ELK1|​pho@Nucleus map
  15. RSK*@Cytoplasm map map RSK*|​pho@Cytoplasm map
  16. MSK*@Nucleus map map MSK*|​pho@Nucleus map
  17. RCAN*@Cytoplasm map map RCAN*|​pho@Cytoplasm map
  18. LRP6@Cytoplasm map map LRP6|​pho|​T1572_pho@Cytoplasm map

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