MAPK1 (mitogen-activated protein kinase 1)

2010-01-01   Seda Tuncay  , Sreeparna Banerjee  

Department of Biological Sciences, Middle East Technical University, Ankara 06531, Turkey

Identity

HGNC
MAPK1
LOCATION
22q11.21
LOCUSID
5594
ALIAS
ERK,ERK-2,ERK2,ERT1,MAPK2,NS13,P42MAPK,PRKM1,PRKM2,p38,p40,p41,p41mapk,p42-MAPK
FUSION GENES
Show Gene Fusions

DNA/RNA

Atlas Image
Diagram of the ERK2 (MAPK1) gene (isoform 1). Exons are represented by open boxes (in scale). Exons 1 to 8 are from the 5 to 3 direction.

Description

According to Entrez Gene ERK2 (MAPK1) gene maps to NC_000022.10 and spans a region of 98.64 kb. According to Spidey mRNA-to-genomic alignment program ERK2 (MAPK1) variant 1 has 8 exons, the sizes being 119, 183, 190, 117, 115, 132, 110, 117 bps (mRNA coordinates).

Transcription

Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene.

Pseudogene

No pseudogenes have been reported for ERK2 (MAPK1).

Proteins

Note

ERK2 (MAPK1) is identified by the specific TEY (Thr-Glu-Tyr) sequence in the activation loop. ERK2 (MAPK1) is activated by dual phosphorylation of tyrosine (Tyr185) and threonine (Thr183) residues which is required for complete activation of the protein. Activated ERK2 (MAPK1) migrates into the nucleus and phosphorylates transcription factors.

Description

ERK2 (MAPK1) is a 41 kDa protein consisting of 360 amino acids. ERK2 (MAPK1) protein is 85% identical to ERK1 (MAPK3) (another MAP kinase family member) and the two proteins have even higher, levels of similarity in their substrate binding regions. ERK2 (MAPK1) possess an acidic patch on the surface-exposed loop L16 of the kinase opposite to its catalytic cleft, which acts as a MAP kinase conserved docking motif (CD site; residues 310-325) which can also be found on activators (MAPKK), inhibitors (PTP-SL (PTPRR) and dual specificity phosphatases) and substrates (ELK-1).

Expression

Ubiquitously expressed with varying levels in different tissues.

Localisation

Subcellular location of ERK2 (MAPK1) protein is the cytoplasm, and the nucleus. Upon activation by dual phosphorylation on its Tyr and Thr residues by upstream kinases, ERK2 (MAPK1) is translocated into the nucleus from cytoplasm where it phosphorylates its nuclear targets.

Function

Being one of the most studied cytoplasmic signaling pathways, the ERK pathway is activated via GTP-loading of RAS at the plasma membrane and sequential activation of a series of protein kinases. Activated RAS recruits the RAF family of kinases such as RAF1 to the plasma membrane which in turn acts as a MAPKKK and activates MAP kinase/ERK kinase 1 and 2 (MEK1 (MAP2K1) and MEK2 (MAP2K2)) by serine phosphorylation. MEK1/2 catalyze the phosphorylation of ERK1 (MAPK3) and ERK2 (MAPK1). Activated ERK1/2 (MAPK3/1) phosphorylates many different substrates involved in various cellular responses from cytoskeletal changes to gene transcription.
It has been shown that activation of ERK1/2 (MAPK3/1) is crucial for cyclin D1 induction, providing a molecular link between ERK signaling and cell cycle control as cyclin D1 gene is essential for G1 to S-phase progression.
In response to Angiotensin II, ERK1/2 (MAPK3/1) regulates cell proliferation by either one of two signaling pathways which are heterotrimeric G protein/PKC zeta-dependent signaling and SRC/YES1/FYN signaling. ERK1/2 (MAPK3/1) phosphorylates specific transcription factors ELK-1 (leading to c-FOS transcriptional activity) following its translocation into the nucleus due to heterotrimeric G protein/PKC zeta-dependent signaling. Due to its phosphorylation in the cytoplasm by SRC/YES1/FYN signaling, ERK1/2 complexes with RSK2 (RPS6KA), which in turn becomes activated and translocates into the nucleus to modulate c-FOS transcription and c-FOS protein activity.
The ERK pathway has been found to be responsible for the phosphorylation of BCL2 that contributes to cell survival, the suppression of the apoptotic effect of BAD, the up-regulation of the antiapoptotic protein MCL-1. Moreover, it has been also shown that ERK1/2 is one of the regulators of TP53 protein accumulation and activation during the DNA damage response.
ERK1/2 induces expression of PAI-1 (plasminogen activator type-1 inhibitor) which is closely associated with dynamic changes in cellular morphology and shape-altering physiologic processes.
CIITA is a critical transcription factor for the initiation of the expression of MHC class II genes and their subsequent induction of the immune response. Studies have indicated that ERK1/2 (MAPK3/1) negatively regulates CIITA by blocking expression of the CIITA gene and/or by phosphorylating CIITA at residues including serine 288, resulting in the loss of CIITA transactivation potential by enabling it to interact with CRM1 (XPO1) which causes export of CIITA protein from the nucleus.

Homology

- P. troglodytes, mitogen-activated protein kinase 1, MAPK1
- C. lupus familiaris, mitogen-activated protein kinase 1, MAPK1
- B. taurus, mitogen-activated protein kinase 1, MAPK1
- M. musculus, mitogen-activated protein kinase 1, MAPK1
- R. norvegicus, mitogen-activated protein kinase 1, MAPK1
- G. gallus, mitogen-activated protein kinase 1, MAPK1
- D. rerio, mitogen-activated protein kinase 1, MAPK1
- D. melanogaster, rl, rolled
- A. gambiae, AgaP_AGAP009207, AGAP009207-PA
- C. elegans, mpk-1, MAP Kinase
- S. cerevisiae, KSS1, Kss1p
- K. lactis, KLLA0A02497g, hypothetical protein
- E. gossypii, AGOS_ACL191C, ACL191Cp
- A. thaliana, ATMPK2, ATMPK2 (ARABIDOPSIS THALIANA MITOGE...)
- A. thaliana, ATMPK1, ATMPK1 (MITOGEN-ACTIVATED PROTEIN K...)
- O. sativa, Os02g0148100, hypothetical protein
- O. sativa, Os06g0699400, hypothetical protein
- P. falciparum, PF11_0147, mitogen-activated protein kinase 2

Implicated in

Entity name
Various diseases
Disease
Although ERK1-/- mice are not embryonic lethal, ERK2-/- mice are. Thus, the ERK2 protein appears to be essential for viability; although dysregulation of the gene/protein expression has been implicated in a number of diseases. Specifically,ERK2 was found to be activated (phosphorylated) in the presence of aspirin triggered lipoxin (ATL-1), a molecule needed for the resolution of inflammation. The activated ERK2 resulted in the survival of mononuclear phagocytes which then exhibit nonphlogistic activities. Additionally, ERK2, but not ERK1, was shown to be constitutively activated by BCR/ABL1 in chronic myelogenous leukemia and implicated in the acquired resistance to imatinib mesylate.
Oncogenesis
Elevated and constitutive activation of ERK1/2 has been detected in a large number of human tumors; including colon, kidney, gastric, prostate, breast, non-small cell lung cancer, bladder, chondrosarcomas and glioblastoma multiforme which show especially high frequencies of kinase activation. The reason for constitutive activation of the ERK pathway in the majority of tumor cells seems to be due to a disorder in RAF, RAS, EGFR or other upstream signaling molecules. In addition, several studies have shown that the ERK-MAPK pathway can directly promote cell motility and the migration of tumor cells.
Entity name
Gastric cancer
Note
Epidermal growth factor (EGF) and urokinase plasminogen activator receptor (uPAR (PLAUR)) are elevated in human gastric cancers and it has been shown that uPAR expression is induced by EGF via ERK1/2 as well as AP-1 (JUN) and NF-kB signaling pathways which in turn, stimulates cell invasiveness in human gastric cancer AGS cells.
Entity name
Breast cancer
Note
In breast cancer patients, ERK1/2 has been found to be heavily phosphorylated on tyrosyl residues and have a 5-10 fold elevated activity compared to benign conditions (fibroadenoma and fibrocystic disease). Localization studies showed that hyperexpressed ERK1/2 mRNA localized to malignant epithelial cells. Furthermore, hyperexpression of ERK1/2 mRNA (5-20 fold) was also observed in metastatic cells within the lymph nodes of breast cancer patients. In addition, in a recent study it was also shown that phosphorylated ERK1/2 levels were significantly high in breast cancer cell lines with high metastatic potential compared to non metastatic breast cancer cell lines. Beta-catenin, cyclin D1, and survivin have been shown to be downstream effectors of pERK1/2, while G1/0 proteins, phospholipase C, and protein kinase C serve as upstream activators of pERK1/2 in those cells.
Entity name
Colorectal cancer
Note
Several lines of evidence indicate that overexpression and activation of ERK-MAPK pathway play an important part in progression of colorectal cancer. The constitutive activation of the RAF/MEK/ERK has been shown to be necessary for RAS-induced transformation of HT1080 human colon carcinoma cell line.
Entity name
Non-small-cell lung cancer
Note
It has been found that nuclear and cytoplasmic ERK1/2 activation positively correlates with the stage and lymph node metastases in lung cancer. Therefore ERK1/2 is associated with advanced and aggressive NSCLC tumors.
Entity name
Bladder cancer
Note
ERK1/2 has been shown to mediate TNF-alpha-induced MMP-9 expression by regulating the binding activity of the transcription factors, NF-kB, AP-1 and SP-1, in urinary bladder cancer HT1376 cells.
Entity name
Glioblastoma multiforme
Note
The activation of ERK1/2 has been implicated in different pathobiological processes of GBM which is the most common and malignant brain tumor. The ERK1/2 activation has been linked to EGFR overexpression and hypermethylation of 9p21 locus.
Entity name
Prostate cancer
Note
In prostate tumors, the level of activated MAP kinase were found to be increased with increasing Gleason score and tumor stage while nonneoplastic prostate tissue showed little or no staining with activated MAP kinase antiserum.
Entity name
Kidney cancer
Note
In a high number of human renal cancers ERK1/2 has been found to be constitutively activated. Moreover, ERK1/2 activation was observed more frequently with high-grade renal cancer cells (RCC) compared to low-grade RCC.
Entity name
Chondrosarcomas
Note
Activation of the JNK (MAPK8) and ERK signal transduction pathways have been shown to increase the activity and expression levels of their downstream effectors, transcription factors AP-1 and RUNX2. These transcription factors, in turn, stimulate genes that are involved in chondroblast cell biology, ultimately inducing chondroblastic tumorigenesis.
Entity name
Cardiac hypertrophy
Note
It has been implicated that ERK1/2 mediate cardiac hypertrophy, which is a major risk factor for the development of arrhythmias, heart failure and sudden death.

Article Bibliography

Pubmed IDLast YearTitleAuthors
195684372009ERK2, but not ERK1, mediates acquired and "de novo" resistance to imatinib mesylate: implication for CML therapy.Aceves-Luquero CI et al
190207432008EGF stimulates uPAR expression and cell invasiveness through ERK, AP-1, and NF-kappaB signaling in human gastric carcinoma cells.Baek MK et al
156774982005The extracellular signal-regulated kinase isoform ERK1 is specifically required for in vitro and in vivo adipogenesis.Bost F et al
90997351997Regulation of peroxisome proliferator-activated receptor gamma activity by mitogen-activated protein kinase.Camp HS et al
158633802005The MAPK signalling pathways and colorectal cancer.Fang JY et al
99270311999Activation of mitogen-activated protein kinase associated with prostate cancer progression.Gioeli D et al
167235112006ERK1/2 regulates ANG II-dependent cell proliferation via cytoplasmic activation of RSK2 and nuclear activation of elk1.Godeny MD et al
152032212004Promoter analysis of the human p44 mitogen-activated protein kinase gene (MAPK3): transcriptional repression under nonproliferating conditions.Hernández R et al
99898331999Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors.Hoshino R et al
87028071996Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway.Lavoie JN et al
184102772008The activation of ERK1/2 MAP kinases in glioblastoma pathobiology and its relationship with EGFR amplification.Lopez-Gines C et al
196661372009Cardiac hypertrophy: targeting Raf/MEK/ERK1/2-signaling.Lorenz K et al
98113321998In situ visualization of intratumor growth factor signaling: immunohistochemical localization of activated ERK/MAP kinase in glial neoplasms.Mandell JW et al
173955902007Minocycline down-regulates MHC II expression in microglia and macrophages through inhibition of IRF-1 and protein kinase C (PKC)alpha/betaII.Nikodemova M et al
76642951995Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma.Oka H et al
163241932005The MAPK-AP-1/-Runx2 signalling axes are implicated in chondrosarcoma pathobiology either independently or via up-regulation of VEGF.Papachristou DJ et al
112948222001Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions.Pearson G et al
109587922000Effect of extracellular signal-regulated kinase on p53 accumulation in response to cisplatin.Persons DL et al
145022232003An essential function of the mitogen-activated protein kinase Erk2 in mouse trophoblast development.Saba-El-Leil MK et al
121180652002MEK/ERK pathway mediates cell-shape-dependent plasminogen activator inhibitor type 1 gene expression upon drug-induced disruption of the microfilament and microtubule networks.Samarakoon R et al
76013371995The MAPK signaling cascade.Seger R et al
200047342010A synthetic analog of 15-epi-lipoxin A4 inhibits human monocyte apoptosis: involvement of ERK-2 and PI3-kinase.Simões RL et al
91199901997Hyperexpression of mitogen-activated protein kinase in human breast cancer.Sivaraman VS et al
117115382002Two clusters of residues at the docking groove of mitogen-activated protein kinases differentially mediate their functional interaction with the tyrosine phosphatases PTP-SL and STEP.Tárrega C et al
161480062005ERK2 shows a restrictive and locally selective mechanism of recognition by its tyrosine phosphatase inactivators not shared by its activator MEK1.Tárrega C et al
149972062004ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours.Vicent S et al
182450892008Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator.Voong LN et al

Other Information

Locus ID:

NCBI: 5594
MIM: 176948
HGNC: 6871
Ensembl: ENSG00000100030

Variants:

dbSNP: 5594
ClinVar: 5594
TCGA: ENSG00000100030
COSMIC: MAPK1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000100030ENST00000215832P28482
ENSG00000100030ENST00000215832Q1HBJ4
ENSG00000100030ENST00000398822P28482
ENSG00000100030ENST00000398822Q1HBJ4
ENSG00000100030ENST00000544786P28482

Expression (GTEx)

0
10
20
30
40
50
60
70
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
ErbB signaling pathwayKEGGko04012
Autophagy - animalKEGGko04140
mTOR signaling pathwayKEGGko04150
ApoptosisKEGGko04210
Dorso-ventral axis formationKEGGko04320
TGF-beta signaling pathwayKEGGko04350
Axon guidanceKEGGko04360
VEGF signaling pathwayKEGGko04370
Focal adhesionKEGGko04510
Adherens junctionKEGGko04520
Gap junctionKEGGko04540
Toll-like receptor signaling pathwayKEGGko04620
Natural killer cell mediated cytotoxicityKEGGko04650
T cell receptor signaling pathwayKEGGko04660
B cell receptor signaling pathwayKEGGko04662
Fc epsilon RI signaling pathwayKEGGko04664
Long-term potentiationKEGGko04720
Long-term depressionKEGGko04730
Regulation of actin cytoskeletonKEGGko04810
Insulin signaling pathwayKEGGko04910
GnRH signaling pathwayKEGGko04912
Progesterone-mediated oocyte maturationKEGGko04914
MelanogenesisKEGGko04916
Type II diabetes mellitusKEGGko04930
Alzheimer's diseaseKEGGko05010
Colorectal cancerKEGGko05210
Renal cell carcinomaKEGGko05211
Pancreatic cancerKEGGko05212
Endometrial cancerKEGGko05213
GliomaKEGGko05214
Prostate cancerKEGGko05215
Thyroid cancerKEGGko05216
MelanomaKEGGko05218
Bladder cancerKEGGko05219
Chronic myeloid leukemiaKEGGko05220
Acute myeloid leukemiaKEGGko05221
Non-small cell lung cancerKEGGko05223
MAPK signaling pathwayKEGGhsa04010
ErbB signaling pathwayKEGGhsa04012
Autophagy - animalKEGGhsa04140
mTOR signaling pathwayKEGGhsa04150
ApoptosisKEGGhsa04210
TGF-beta signaling pathwayKEGGhsa04350
Axon guidanceKEGGhsa04360
VEGF signaling pathwayKEGGhsa04370
Focal adhesionKEGGhsa04510
Adherens junctionKEGGhsa04520
Gap junctionKEGGhsa04540
Toll-like receptor signaling pathwayKEGGhsa04620
Natural killer cell mediated cytotoxicityKEGGhsa04650
T cell receptor signaling pathwayKEGGhsa04660
B cell receptor signaling pathwayKEGGhsa04662
Fc epsilon RI signaling pathwayKEGGhsa04664
Long-term potentiationKEGGhsa04720
Long-term depressionKEGGhsa04730
Regulation of actin cytoskeletonKEGGhsa04810
Insulin signaling pathwayKEGGhsa04910
GnRH signaling pathwayKEGGhsa04912
MelanogenesisKEGGhsa04916
Type II diabetes mellitusKEGGhsa04930
Alzheimer's diseaseKEGGhsa05010
ShigellosisKEGGhsa05131
Pathways in cancerKEGGhsa05200
Colorectal cancerKEGGhsa05210
Renal cell carcinomaKEGGhsa05211
Pancreatic cancerKEGGhsa05212
Endometrial cancerKEGGhsa05213
GliomaKEGGhsa05214
Prostate cancerKEGGhsa05215
Thyroid cancerKEGGhsa05216
MelanomaKEGGhsa05218
Bladder cancerKEGGhsa05219
Chronic myeloid leukemiaKEGGhsa05220
Acute myeloid leukemiaKEGGhsa05221
Non-small cell lung cancerKEGGhsa05223
Vascular smooth muscle contractionKEGGhsa04270
Chemokine signaling pathwayKEGGko04062
Vascular smooth muscle contractionKEGGko04270
Chemokine signaling pathwayKEGGhsa04062
Neurotrophin signaling pathwayKEGGko04722
Prion diseasesKEGGko05020
Neurotrophin signaling pathwayKEGGhsa04722
Prion diseasesKEGGhsa05020
Fc gamma R-mediated phagocytosisKEGGko04666
Dorso-ventral axis formationKEGGhsa04320
Fc gamma R-mediated phagocytosisKEGGhsa04666
Progesterone-mediated oocyte maturationKEGGhsa04914
NOD-like receptor signaling pathwayKEGGko04621
NOD-like receptor signaling pathwayKEGGhsa04621
Oocyte meiosisKEGGko04114
Oocyte meiosisKEGGhsa04114
Aldosterone-regulated sodium reabsorptionKEGGko04960
Aldosterone-regulated sodium reabsorptionKEGGhsa04960
LeishmaniasisKEGGko05140
LeishmaniasisKEGGhsa05140
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
ToxoplasmosisKEGGko05145
ToxoplasmosisKEGGhsa05145
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
TuberculosisKEGGko05152
TuberculosisKEGGhsa05152
Glutamatergic synapseKEGGko04724
Glutamatergic synapseKEGGhsa04724
Influenza AKEGGko05164
Influenza AKEGGhsa05164
Cholinergic synapseKEGGhsa04725
PertussisKEGGko05133
PertussisKEGGhsa05133
Salmonella infectionKEGGko05132
Salmonella infectionKEGGhsa05132
Serotonergic synapseKEGGhsa04726
Retrograde endocannabinoid signalingKEGGhsa04723
Retrograde endocannabinoid signalingKEGGko04723
AlcoholismKEGGhsa05034
AlcoholismKEGGko05034
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Hepatitis BKEGGhsa05161
HIF-1 signaling pathwayKEGGhsa04066
Circadian entrainmentKEGGhsa04713
Circadian entrainmentKEGGko04713
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Estrogen signaling pathwayKEGGhsa04915
Estrogen signaling pathwayKEGGko04915
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Ras signaling pathwayKEGGhsa04014
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
Adrenergic signaling in cardiomyocytesKEGGhsa04261
Adrenergic signaling in cardiomyocytesKEGGko04261
FoxO signaling pathwayKEGGhsa04068
Thyroid hormone signaling pathwayKEGGhsa04919
Platelet activationKEGGhsa04611
Oxytocin signaling pathwayKEGGhsa04921
Oxytocin signaling pathwayKEGGko04921
cGMP-PKG signaling pathwayKEGGhsa04022
cGMP-PKG signaling pathwayKEGGko04022
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Central carbon metabolism in cancerKEGGhsa05230
Choline metabolism in cancerKEGGhsa05231
Central carbon metabolism in cancerKEGGko05230
Choline metabolism in cancerKEGGko05231
MAPK (ERK1/2) signalingKEGGhsa_M00687
MAPK (ERK1/2) signalingKEGGM00687
Sphingolipid signaling pathwayKEGGhsa04071
Sphingolipid signaling pathwayKEGGko04071
Neuronal SystemREACTOMER-HSA-112316
Transmission across Chemical SynapsesREACTOMER-HSA-112315
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic CellREACTOMER-HSA-112314
Activation of NMDA receptor upon glutamate binding and postsynaptic eventsREACTOMER-HSA-442755
Post NMDA receptor activation eventsREACTOMER-HSA-438064
CREB phosphorylation through the activation of RasREACTOMER-HSA-442742
RSK activationREACTOMER-HSA-444257
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
PIP3 activates AKT signalingREACTOMER-HSA-1257604
Negative regulation of the PI3K/AKT networkREACTOMER-HSA-199418
Innate Immune SystemREACTOMER-HSA-168249
Toll-Like Receptors CascadesREACTOMER-HSA-168898
Toll Like Receptor 10 (TLR10) CascadeREACTOMER-HSA-168142
MyD88 cascade initiated on plasma membraneREACTOMER-HSA-975871
MAP kinase activation in TLR cascadeREACTOMER-HSA-450294
MAPK targets/ Nuclear events mediated by MAP kinasesREACTOMER-HSA-450282
ERK/MAPK targetsREACTOMER-HSA-198753
ERKs are inactivatedREACTOMER-HSA-202670
Activation of the AP-1 family of transcription factorsREACTOMER-HSA-450341
Toll Like Receptor 3 (TLR3) CascadeREACTOMER-HSA-168164
MyD88-independent TLR3/TLR4 cascadeREACTOMER-HSA-166166
TRIF-mediated TLR3/TLR4 signalingREACTOMER-HSA-937061
Toll Like Receptor 5 (TLR5) CascadeREACTOMER-HSA-168176
Toll Like Receptor 7/8 (TLR7/8) CascadeREACTOMER-HSA-168181
MyD88 dependent cascade initiated on endosomeREACTOMER-HSA-975155
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activationREACTOMER-HSA-975138
Toll Like Receptor 9 (TLR9) CascadeREACTOMER-HSA-168138
Toll Like Receptor 4 (TLR4) CascadeREACTOMER-HSA-166016
Activated TLR4 signallingREACTOMER-HSA-166054
MyD88:Mal cascade initiated on plasma membraneREACTOMER-HSA-166058
Toll Like Receptor 2 (TLR2) CascadeREACTOMER-HSA-181438
Toll Like Receptor TLR1:TLR2 CascadeREACTOMER-HSA-168179
Toll Like Receptor TLR6:TLR2 CascadeREACTOMER-HSA-168188
Advanced glycosylation endproduct receptor signalingREACTOMER-HSA-879415
Fcgamma receptor (FCGR) dependent phagocytosisREACTOMER-HSA-2029480
Regulation of actin dynamics for phagocytic cup formationREACTOMER-HSA-2029482
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
MAP2K and MAPK activationREACTOMER-HSA-5674135
Negative regulation of MAPK pathwayREACTOMER-HSA-5675221
Negative feedback regulation of MAPK pathwayREACTOMER-HSA-5674499
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Role of LAT2/NTAL/LAB on calcium mobilizationREACTOMER-HSA-2730905
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
Growth hormone receptor signalingREACTOMER-HSA-982772
HemostasisREACTOMER-HSA-109582
Platelet activation, signaling and aggregationREACTOMER-HSA-76002
Thrombin signalling through proteinase activated receptors (PARs)REACTOMER-HSA-456926
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
GAB1 signalosomeREACTOMER-HSA-180292
Signaling by FGFRREACTOMER-HSA-190236
Signaling by FGFR1REACTOMER-HSA-5654736
Negative regulation of FGFR1 signalingREACTOMER-HSA-5654726
Spry regulation of FGF signalingREACTOMER-HSA-1295596
Signaling by FGFR2REACTOMER-HSA-5654738
Negative regulation of FGFR2 signalingREACTOMER-HSA-5654727
Signaling by FGFR3REACTOMER-HSA-5654741
Negative regulation of FGFR3 signalingREACTOMER-HSA-5654732
Signaling by FGFR4REACTOMER-HSA-5654743
Negative regulation of FGFR4 signalingREACTOMER-HSA-5654733
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
SOS-mediated signallingREACTOMER-HSA-112412
Signal attenuationREACTOMER-HSA-74749
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
PI3K/AKT activationREACTOMER-HSA-198203
Nuclear Events (kinase and transcription factor activation)REACTOMER-HSA-198725
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFA-VEGFR2 PathwayREACTOMER-HSA-4420097
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
RAF-independent MAPK1/3 activationREACTOMER-HSA-112409
MAPK1 (ERK2) activationREACTOMER-HSA-112411
Signaling by Rho GTPasesREACTOMER-HSA-194315
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases Activate WASPs and WAVEsREACTOMER-HSA-5663213
Signaling by GPCRREACTOMER-HSA-372790
Opioid SignallingREACTOMER-HSA-111885
G-protein mediated eventsREACTOMER-HSA-112040
PLC beta mediated eventsREACTOMER-HSA-112043
Ca-dependent eventsREACTOMER-HSA-111996
phospho-PLA2 pathwayREACTOMER-HSA-111995
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
M PhaseREACTOMER-HSA-68886
Mitotic ProphaseREACTOMER-HSA-68875
Golgi Cisternae Pericentriolar Stack ReorganizationREACTOMER-HSA-162658
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
L1CAM interactionsREACTOMER-HSA-373760
Recycling pathway of L1REACTOMER-HSA-437239
Signal transduction by L1REACTOMER-HSA-445144
Cellular responses to stressREACTOMER-HSA-2262752
Cellular response to heat stressREACTOMER-HSA-3371556
Regulation of HSF1-mediated heat shock responseREACTOMER-HSA-3371453
Cellular SenescenceREACTOMER-HSA-2559583
Oncogene Induced SenescenceREACTOMER-HSA-2559585
Oxidative Stress Induced SenescenceREACTOMER-HSA-2559580
Senescence-Associated Secretory Phenotype (SASP)REACTOMER-HSA-2559582
Phospholipase D signaling pathwayKEGGko04072
Phospholipase D signaling pathwayKEGGhsa04072
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
PI5P, PP2A and IER3 Regulate PI3K/AKT SignalingREACTOMER-HSA-6811558
EGFR tyrosine kinase inhibitor resistanceKEGGko01521
Platinum drug resistanceKEGGko01524
Endocrine resistanceKEGGko01522
Platinum drug resistanceKEGGhsa01524
EGFR tyrosine kinase inhibitor resistanceKEGGhsa01521
Endocrine resistanceKEGGhsa01522
RET signalingREACTOMER-HSA-8853659
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224
Neutrophil degranulationREACTOMER-HSA-6798695
Oncogenic MAPK signalingREACTOMER-HSA-6802957
Signaling by RAS mutantsREACTOMER-HSA-6802949
Signaling by high-kinase activity BRAF mutantsREACTOMER-HSA-6802948
Signaling by moderate kinase activity BRAF mutantsREACTOMER-HSA-6802946
Paradoxical activation of RAF signaling by kinase inactive BRAFREACTOMER-HSA-6802955
Signaling by BRAF and RAF fusionsREACTOMER-HSA-6802952
Th1 and Th2 cell differentiationKEGGko04658
Th1 and Th2 cell differentiationKEGGhsa04658
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659
IL-17 signaling pathwayKEGGko04657
IL-17 signaling pathwayKEGGhsa04657
Apelin signaling pathwayKEGGhsa04371

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA248NFKB1GenePathwayassociated
PA27749ELK1GenePathwayassociated
PA27902ETS1GenePathwayassociated
PA28212FOSGenePathwayassociated
PA284MAP2K7GenePathwayassociated20124951
PA296RELAGenePathwayassociated
PA30006JUNGenePathwayassociated
PA30584MAP2K1GenePathwayassociated20124951, 28362716
PA30587MAP2K2GenePathwayassociated20124951, 28362716
PA30588MAP2K3GenePathwayassociated20124951
PA30589MAP2K4GenePathwayassociated20124951
PA30590MAP2K5GenePathwayassociated20124951
PA30591MAP2K6GenePathwayassociated20124951
PA31353MYCGenePathwayassociated
PA31600NFKB2GenePathwayassociated
PA337STAT3GenePathwayassociated
PA33748PRKACAGenePathwayassociated
PA33749PRKACBGenePathwayassociated
PA33750PRKACGGenePathwayassociated
PA338STAT5AGenePathwayassociated
PA36042SP1GenePathwayassociated
PA36111SRCGenePathwayassociated
PA36183STAT1GenePathwayassociated
PA36184STAT2GenePathwayassociated
PA36185STAT4GenePathwayassociated
PA36186STAT5BGenePathwayassociated
PA40GRK2GenePathwayassociated
PA41GRK3GenePathwayassociated
PA59ARRB1GenePathwayassociated
PA60ARRB2GenePathwayassociated
PA62ATP1A1GenePathwayassociated23788015
PA7000sorafenibChemicalPathwayassociated20124951

References

Pubmed IDYearTitleCitations
370414232024miR-4529-3p Promotes the Progression of Retinoblastoma by Inhibiting RB1 Expression and Activating the ERK Signaling Pathway.0
372371352024ERK/PKM2 Is Mediated in the Warburg Effect and Cell Proliferation in Arsenic-Induced Human L-02 Hepatocytes.0
372601242024LncRNA PVT1 inhibits endothelial cells apoptosis in coronary heart disease through regulating MAPK1 expression via miR-532-3p.0
373180322024miR-200a-3p regulates epithelial-mesenchymal transition and inflammation in chronic rhinosinusitis with nasal polyps by targeting ZEB1 via ERK/p38 pathway.0
374625322024Leukocyte Ig-like receptor A3 facilitates inflammation, migration and invasion of synovial tissue-derived fibroblasts via ERK/JNK activation.1
380489192024Progestins and breast cancer hallmarks: The role of the ERK1/2 and JNK pathways in estrogen receptor positive breast cancer cells.0
381417692024LncNFYB promotes the proliferation of rheumatoid arthritis fibroblast-like synoviocytes via LncNFYB/ANXA2/ERK1/2 axis.0
381696252024MAPK1 Mediates MAM Disruption and Mitochondrial Dysfunction in Diabetic Kidney Disease via the PACS-2-Dependent Mechanism.0
381815852024FNDC4 reduces inflammation, proliferation, invasion and migration of rheumatoid synovial cells by inhibiting CCL2/ERK signaling.0
382160902024EID3 inhibits the osteogenic differentiation of periodontal ligament stem cells and mediates the signal transduction of TAZ-EID3-AKT/MTOR/ERK.0
382617432024IL-17 promotes IL-18 production via the MEK/ERK/miR-4492 axis in osteoarthritis synovial fibroblasts.0
383019102024PP4R1 promotes glycolysis and gallbladder cancer progression through facilitating ERK1/2 mediated PKM2 nuclear translocation.0
384300292024Circ-LDLRAD3/miR-655-3p/MAPK1 axis enhances cell migration and invasion in papillary thyroid carcinoma.0
384668342024Inhibition of HSP20 Ameliorates Steatotic Liver Disease by Stimulating ERK2-Dependent Autophagy.0
385818592024ALOX15B controls macrophage cholesterol homeostasis via lipid peroxidation, ERK1/2 and SREBP2.0

Citation

Seda Tuncay ; Sreeparna Banerjee

MAPK1 (mitogen-activated protein kinase 1)

Atlas Genet Cytogenet Oncol Haematol. 2010-01-01

Online version: http://atlasgeneticsoncology.org/gene/41288/tumors-explorer/haematological-explorer/js/lib/zoomerang.js