MAP kinase signalling pathways
MAP kinase signalling pathways. Major pathways that transfer extracellular signals to the nucleus are the MAP kinase signalling pathways. The extracellular stimuli may be heterogeneous, deriving from exposure of cells to growth factors, phorbol esters, cytokines, or cellular stresses, such as osmotic shock and γ-irradiation. In principal, the Ras-Raf-MEK-ERK pathway transduces mitogenic signals involved in cellular proliferation or differentiation. The JNK/SAPK and p38 pathways regulate the cellular inflammatory or stress response. There are interactions between both pathways on MAPK kinase kinase (MAPKKK) levels immediately upstream of MEK (not indicated in the presented scheme). The downstream targets of the MAP kinase signalling pathways are the MAP kinases, ERK, JNK/SAPK and p38, which directly or indirectly interfere with transcription factors, such as Elk-1, ATF2 or cJun for activation of gene transcription. Upstream signalling components include the family of Rho GTPases such as Rho, Rac and Cdc42 which interfere with MAPKKK. Cellular stresses such as hypoxia may activate JNK/SAPK and p38 pathways which exert influence on cJun and ATF-2 activation.
Publication
Molecular responses to hypoxia in tumor cells. (2003)
Manfred Kunz, et al. Mol Cancer. 2003;2:23-23. Figure: F1.
All organisms
Rattus norvegicus
Mus musculus
Homo sapiens
Gallus gallus
Oryctolagus cuniculus
Drosophila melanogaster
Danio rerio
Organism
Group
Word
Match
Source
NCBI Symbol
NCBI ID
Rattus norvegicus
Rodents
cdc42
CDC42
ncbigene_symbol
Cdc42
64465
Rattus norvegicus
Rodents
Rho
RHO
ncbigene_symbol
Rho
24717
Rattus norvegicus
Rodents
MKK3
MKK3
ncbigene_synonym
Map2k3
303200
Rattus norvegicus
Rodents
MKK6
MKK6
ncbigene_synonym
Map2k6
114495
Rattus norvegicus
Rodents
MKK4/MKK7
MKK7
ncbigene_synonym
Map2k7
363855
Rattus norvegicus
Rodents
MKK4/MKK7
MKK4
ncbigene_synonym
Map2k4
287398
Rattus norvegicus
Rodents
p38
P38
ncbigene_synonym
Mapk14
81649
Rattus norvegicus
Rodents
JNK
JNK
ncbigene_synonym
Mapk8
116554
Rattus norvegicus
Rodents
SAPK
SAPK
ncbigene_synonym
Mapk9
50658
Rattus norvegicus
Rodents
ERK1
ERK1
ncbigene_synonym
Mapk3
50689
Rattus norvegicus
Rodents
ERK1/2
ERK2
ncbigene_synonym
Mapk1
116590
Rattus norvegicus
Rodents
ATF2
ATF2
ncbigene_symbol
Atf2
81647
Rattus norvegicus
Rodents
Elk-1
ELK1
ncbigene_symbol
Elk1
314436
Rattus norvegicus
Rodents
Elk-1
ELK1
ncbigene_synonym
Kcnh8
246325
Rattus norvegicus
Rodents
Ets1/2
ETS2
ncbigene_symbol
Ets2
304063
Rattus norvegicus
Rodents
Ets1/2
ETS1
ncbigene_symbol
Ets1
24356
Rattus norvegicus
Rodents
MEF-2c
MEF2C
ncbigene_symbol
Mef2c
499497
Rattus norvegicus
Rodents
CREB
CREB
ncbigene_synonym
Creb1
81646
Rattus norvegicus
Rodents
c-Jun
JUN
ncbigene_symbol
Jun
24516
Mus musculus
Rodents
cdc42
CDC42
ncbigene_symbol
Cdc42
12540
Mus musculus
Rodents
Rho
RHO
ncbigene_symbol
Rho
212541
Mus musculus
Rodents
Rho
RHO
ncbigene_synonym
Rhod
11854
Mus musculus
Rodents
Rho
RHO
ncbigene_synonym
Ea2
104194
Mus musculus
Rodents
Rac
RAC
ncbigene_synonym
Akt1
11651
Mus musculus
Rodents
Ras
RAS
ncbigene_symbol
ras
19412
Mus musculus
Rodents
Ras
RAS
ncbigene_synonym
Hras
15461
Mus musculus
Rodents
Ras
RAS
ncbigene_synonym
Kras
16653
Mus musculus
Rodents
Ras
RAS
ncbigene_synonym
Rem1
19700
Mus musculus
Rodents
MKK3
MKK3
ncbigene_synonym
Map2k3
26397
Mus musculus
Rodents
MKK6
MKK6
ncbigene_synonym
Map2k6
26399
Mus musculus
Rodents
MKK4/MKK7
MKK7
ncbigene_synonym
Map2k7
26400
Mus musculus
Rodents
MKK4/MKK7
MKK4
ncbigene_synonym
Map2k4
26398
Mus musculus
Rodents
Raf
RAF
ncbigene_synonym
Zhx2
387609
Mus musculus
Rodents
MEK
MEK
ncbigene_synonym
Mdk
17242
Mus musculus
Rodents
p38
P38
ncbigene_synonym
Crk
12928
Mus musculus
Rodents
p38
P38
ncbigene_synonym
Grap2
17444
Mus musculus
Rodents
p38
P38
ncbigene_synonym
Syp
20977
Mus musculus
Rodents
p38
P38
ncbigene_synonym
Mapk14
26416
Mus musculus
Rodents
p38
P38
ncbigene_synonym
Ahsa1
217737
Mus musculus
Rodents
JNK
JNK
ncbigene_synonym
Mapk8
26419
Mus musculus
Rodents
ERK1
ERK1
ncbigene_synonym
Mapk3
26417
Mus musculus
Rodents
ERK1/2
ERK2
ncbigene_synonym
Mapk1
26413
Mus musculus
Rodents
ATF2
ATF2
ncbigene_symbol
Atf2
11909
Mus musculus
Rodents
Elk-1
ELK-1
ncbigene_synonym
Elk1
13712
Mus musculus
Rodents
Ets1/2
ETS2
ncbigene_symbol
Ets2
23872
Mus musculus
Rodents
Ets1/2
ETS1
ncbigene_symbol
Ets1
23871
Mus musculus
Rodents
MEF-2c
MEF2C
ncbigene_symbol
Mef2c
17260
Mus musculus
Rodents
CREB
CREB
ncbigene_synonym
Creb1
12912
Mus musculus
Rodents
c-Jun
C-JUN
ncbigene_synonym
Jun
16476
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
ANGPT1
284
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
ANGPT2
285
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
ANGPT4
51378
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
AREG
374
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
BDNF
627
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
CSF1
1435
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
EFNA1
1942
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
EFNA2
1943
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
EFNA3
1944
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
EFNA4
1945
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
EFNA5
1946
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
EGF
1950
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
EREG
2069
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF1
2246
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF10
2255
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF16
8823
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF17
8822
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF18
8817
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF19
9965
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF2
2247
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF20
26281
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF21
26291
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF22
27006
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF23
8074
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF3
2248
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF4
2249
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF5
2250
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF6
2251
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF7
2252
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF8
2253
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FGF9
2254
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
FLT3LG
2323
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
HGF
3082
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
IGF1
3479
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
IGF2
3481
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
INS
3630
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
KITLG
4254
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
NGF
4803
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
NTF3
4908
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
NTF4
4909
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
PDGFA
5154
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
PDGFB
5155
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
PDGFC
56034
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
PDGFD
80310
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
PGF
5228
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
TGFA
7039
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
VEGFA
7422
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
VEGFB
7423
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
VEGFC
7424
Homo sapiens
Primates
Growthfactors,
GROWTHFACTOR
famplex_relations
VEGFD
2277
Homo sapiens
Primates
cdc42
CDC42
ncbigene_symbol
CDC42
998
Homo sapiens
Primates
Rho
RHO
ncbigene_symbol
RHO
6010
Homo sapiens
Primates
Rho
RHO
ncbigene_synonym
RHOD
29984
Homo sapiens
Primates
Rho
RHO
famplex_relations
RHOA
387
Homo sapiens
Primates
Rho
RHO
famplex_relations
RHOB
388
Homo sapiens
Primates
Rho
RHO
famplex_relations
RHOC
389
Homo sapiens
Primates
Rac
RAC
ncbigene_synonym
AKT1
207
Homo sapiens
Primates
Rac
RAC
famplex_relations
RAC1
5879
Homo sapiens
Primates
Rac
RAC
famplex_relations
RAC2
5880
Homo sapiens
Primates
Rac
RAC
famplex_relations
RAC3
5881
Homo sapiens
Primates
Rac
RAC
famplex_relations
RHOG
391
Homo sapiens
Primates
Ras
RAS
famplex_relations
KRAS
3845
Homo sapiens
Primates
Ras
RAS
famplex_relations
HRAS
3265
Homo sapiens
Primates
Ras
RAS
famplex_relations
NRAS
4893
Homo sapiens
Primates
MKK3
MKK3
ncbigene_synonym
MAP2K3
5606
Homo sapiens
Primates
MKK6
MKK6
ncbigene_synonym
MAP2K6
5608
Homo sapiens
Primates
MKK4/MKK7
MKK7
ncbigene_synonym
MAP2K7
5609
Homo sapiens
Primates
MKK4/MKK7
MKK4
ncbigene_synonym
MAP2K4
6416
Homo sapiens
Primates
Raf
RAF
ncbigene_synonym
ZHX2
22882
Homo sapiens
Primates
Raf
RAF
famplex_relations
ARAF
369
Homo sapiens
Primates
Raf
RAF
famplex_relations
BRAF
673
Homo sapiens
Primates
Raf
RAF
famplex_relations
RAF1
5894
Homo sapiens
Primates
MEK
MEK
famplex_relations
MAP2K1
5604
Homo sapiens
Primates
MEK
MEK
famplex_relations
MAP2K2
5605
Homo sapiens
Primates
p38
P38
ncbigene_synonym
CRK
1398
Homo sapiens
Primates
p38
P38
ncbigene_synonym
MAPK14
1432
Homo sapiens
Primates
p38
P38
ncbigene_synonym
MAPK1
5594
Homo sapiens
Primates
p38
P38
ncbigene_synonym
AIMP2
7965
Homo sapiens
Primates
p38
P38
ncbigene_synonym
GRAP2
9402
Homo sapiens
Primates
p38
P38
ncbigene_synonym
AHSA1
10598
Homo sapiens
Primates
p38
P38
ncbigene_synonym
POLDIP2
26073
Homo sapiens
Primates
p38
P38
famplex_relations
MAPK11
5600
Homo sapiens
Primates
p38
P38
famplex_relations
MAPK12
6300
Homo sapiens
Primates
p38
P38
famplex_relations
MAPK13
5603
Homo sapiens
Primates
JNK
JNK
ncbigene_synonym
MAPK8
5599
Homo sapiens
Primates
JNK
JNK
famplex_relations
MAPK9
5601
Homo sapiens
Primates
JNK
JNK
famplex_relations
MAPK10
5602
Homo sapiens
Primates
ERK1
ERK1
ncbigene_synonym
MAPK3
5595
Homo sapiens
Primates
ATF2
ATF2
ncbigene_symbol
ATF2
1386
Homo sapiens
Primates
ATF2
ATF2
ncbigene_synonym
GDNF
2668
Homo sapiens
Primates
Elk-1
ELK1
ncbigene_symbol
ELK1
2002
Homo sapiens
Primates
Elk-1
ELK1
ncbigene_synonym
KCNH4
23415
Homo sapiens
Primates
Elk-1
ELK1
ncbigene_synonym
KCNH8
131096
Homo sapiens
Primates
Ets1/2
ETS2
ncbigene_symbol
ETS2
2114
Homo sapiens
Primates
Ets1/2
ETS1
ncbigene_symbol
ETS1
2113
Homo sapiens
Primates
MEF-2c
MEF2C
ncbigene_symbol
MEF2C
4208
Homo sapiens
Primates
CREB
CREB
ncbigene_synonym
CREB1
1385
Homo sapiens
Primates
CREB
CREB
famplex_relations
CREB3
10488
Homo sapiens
Primates
CREB
CREB
famplex_relations
CREB5
9586
Homo sapiens
Primates
CREB
CREB
famplex_relations
CREB3L1
90993
Homo sapiens
Primates
CREB
CREB
famplex_relations
CREB3L2
64764
Homo sapiens
Primates
CREB
CREB
famplex_relations
CREB3L3
84699
Homo sapiens
Primates
CREB
CREB
famplex_relations
CREB3L4
148327
Homo sapiens
Primates
CREB
CREB
famplex_relations
CREM
1390
Homo sapiens
Primates
CREB
CREB
famplex_relations
ATF1
466
Homo sapiens
Primates
c-Jun
C-JUN
ncbigene_synonym
JUN
3725
Gallus gallus
Vertebrates
cdc42
CDC42
ncbigene_symbol
CDC42
395917
Gallus gallus
Vertebrates
Rho
RHO
ncbigene_symbol
RHO
751791
Gallus gallus
Vertebrates
Rho
RHO
ncbigene_synonym
OPN1MSW
396486
Gallus gallus
Vertebrates
p38
P38
ncbigene_synonym
CRK
107054794
Gallus gallus
Vertebrates
ATF2
ATF2
ncbigene_symbol
ATF2
395727
Gallus gallus
Vertebrates
Ets1/2
ETS2
ncbigene_symbol
ETS2
396250
Gallus gallus
Vertebrates
Ets1/2
ETS1
ncbigene_symbol
ETS1
396235
Gallus gallus
Vertebrates
MEF-2c
MEF2C
ncbigene_symbol
MEF2C
769007
Gallus gallus
Vertebrates
c-Jun
JUN
ncbigene_symbol
JUN
424673
Oryctolagus cuniculus
Mammals
cdc42
CDC42
ncbigene_symbol
CDC42
100008965
Oryctolagus cuniculus
Mammals
Rho
RHO
ncbigene_symbol
RHO
100009200
Oryctolagus cuniculus
Mammals
ATF2
ATF2
ncbigene_symbol
ATF2
100355367
Oryctolagus cuniculus
Mammals
Elk-1
ELK1
ncbigene_symbol
ELK1
100340952
Oryctolagus cuniculus
Mammals
Ets1/2
ETS2
ncbigene_symbol
ETS2
100350788
Oryctolagus cuniculus
Mammals
Ets1/2
ETS1
ncbigene_symbol
ETS1
100009373
Oryctolagus cuniculus
Mammals
MEF-2c
MEF2C
ncbigene_symbol
MEF2C
100345167
Oryctolagus cuniculus
Mammals
c-Jun
C-JUN
ncbigene_synonym
JUN
100008856
Drosophila melanogaster
Invertebrates
cdc42
CDC42
ncbigene_symbol
Cdc42
32981
Drosophila melanogaster
Invertebrates
Rho
RHO
ncbigene_symbol
rho
38168
Drosophila melanogaster
Invertebrates
Rho
RHO
ncbigene_synonym
Bx
32846
Drosophila melanogaster
Invertebrates
Rho
RHO
ncbigene_synonym
Rho1
36775
Drosophila melanogaster
Invertebrates
Rho
RHO
ncbigene_synonym
Lcp65Ab1
48382
Drosophila melanogaster
Invertebrates
Rac
RAC
ncbigene_synonym
Rac1
38146
Drosophila melanogaster
Invertebrates
Rac
RAC
ncbigene_synonym
Rac2
38831
Drosophila melanogaster
Invertebrates
Rac
RAC
ncbigene_synonym
Akt
41957
Drosophila melanogaster
Invertebrates
Rac
RAC
ncbigene_synonym
Mtl
43319
Drosophila melanogaster
Invertebrates
Ras
RAS
ncbigene_symbol
ras
43873
Drosophila melanogaster
Invertebrates
Ras
RAS
ncbigene_synonym
Ras64B
38494
Drosophila melanogaster
Invertebrates
Ras
RAS
ncbigene_synonym
Ras85D
41140
Drosophila melanogaster
Invertebrates
MAPKKK
MAPKKK
ncbigene_synonym
wnd
40143
Drosophila melanogaster
Invertebrates
MKK3
MKK3
ncbigene_synonym
lic
32257
Drosophila melanogaster
Invertebrates
MKK4/MKK7
MKK7
ncbigene_synonym
hep
32256
Drosophila melanogaster
Invertebrates
MKK4/MKK7
MKK4
ncbigene_symbol
Mkk4
41020
Drosophila melanogaster
Invertebrates
Raf
RAF
ncbigene_symbol
Raf
31221
Drosophila melanogaster
Invertebrates
MEK
MEK
ncbigene_synonym
Dsor1
31872
Drosophila melanogaster
Invertebrates
MEK
MEK
ncbigene_synonym
Mtk
36708
Drosophila melanogaster
Invertebrates
p38
P38
ncbigene_synonym
p38b
34780
Drosophila melanogaster
Invertebrates
p38
P38
ncbigene_synonym
Nurf-38
37922
Drosophila melanogaster
Invertebrates
p38
P38
ncbigene_synonym
Ebp
38009
Drosophila melanogaster
Invertebrates
p38
P38
ncbigene_synonym
AIMP2
39690
Drosophila melanogaster
Invertebrates
p38
P38
ncbigene_synonym
p38a
42866
Drosophila melanogaster
Invertebrates
p38
P38
ncbigene_synonym
Hrb87F
48535
Drosophila melanogaster
Invertebrates
p38
P38
ncbigene_synonym
p38c
2768679
Drosophila melanogaster
Invertebrates
JNK
JNK
ncbigene_synonym
bsk
44801
Drosophila melanogaster
Invertebrates
ERK1
ERK1
ncbigene_synonym
rl
3354888
Drosophila melanogaster
Invertebrates
ATF2
ATF2
ncbigene_symbol
Atf-2
37978
Drosophila melanogaster
Invertebrates
ATF2
ATF2
ncbigene_synonym
CG44247
19835727
Drosophila melanogaster
Invertebrates
Ets1/2
ETS1/2
ncbigene_synonym
pnt
42757
Drosophila melanogaster
Invertebrates
MEF-2c
MEF2C
ncbigene_synonym
Mef2
36032
Drosophila melanogaster
Invertebrates
CREB
CREB
ncbigene_synonym
CrebB
32817
Drosophila melanogaster
Invertebrates
CREB
CREB
ncbigene_synonym
CrebA
39682
Drosophila melanogaster
Invertebrates
c-Jun
C-JUN
ncbigene_synonym
Jra
36057
Danio rerio
Vertebrates
cdc42
CDC42
ncbigene_symbol
cdc42
336839
Danio rerio
Vertebrates
cdc42
CDC42
ncbigene_synonym
cdc42l
793158
Danio rerio
Vertebrates
Rho
RHO
ncbigene_symbol
rho
30295
Danio rerio
Vertebrates
Rho
RHO
ncbigene_synonym
rnd2
751645
Danio rerio
Vertebrates
Ras
RAS
ncbigene_synonym
rab1ab
368883
Danio rerio
Vertebrates
MKK3
MKK3
ncbigene_synonym
map2k6
65239
Danio rerio
Vertebrates
MKK4/MKK7
MKK7
ncbigene_synonym
map2k7
560913
Danio rerio
Vertebrates
MKK4/MKK7
MKK4
ncbigene_synonym
map2k4a
403052
Danio rerio
Vertebrates
p38
P38
ncbigene_synonym
mapk14a
65237
Danio rerio
Vertebrates
JNK
JNK
ncbigene_synonym
mapk8b
65236
Danio rerio
Vertebrates
ERK1
ERK1
ncbigene_synonym
mapk3
399480
Danio rerio
Vertebrates
ATF2
ATF2
ncbigene_symbol
atf2
100006516
Danio rerio
Vertebrates
Elk-1
ELK1
ncbigene_symbol
elk1
567895
Danio rerio
Vertebrates
Ets1/2
ETS2
ncbigene_symbol
ets2
326672
Danio rerio
Vertebrates
Ets1/2
ETS1
ncbigene_symbol
ets1
280651
Danio rerio
Vertebrates
MEF-2c
MEF2C
ncbigene_synonym
mef2ca
30575
Danio rerio
Vertebrates
c-Jun
C-JUN
ncbigene_synonym
jun
335916
Disease mentions
Word
Match
MeSH
Name
DOID
Cancer
NA
Cardiomyopathy
NA
Noonan syndrome
NA