Summary

Name MAPK8
Full Name Mitogen-activated protein kinase 8
Synonyms MAP kinase 8, MAPK 8, JNK-46, Stress-activated protein kinase 1c, SAPK1c, Stress-activated protein kinase JNK1, c-Jun N-terminal kinase 1 | JNK1, PRKM8, SAPK1, SAPK1C
Primary ID P45983
Links - -
Type protein
Relations 173
Pathways Acute Myeloid Leukemia, COVID-19 Causal Network, EGFR Signaling, FLT3-ITD in AML, Glucocorticoid receptor Signaling, Macrophage polarization, SAPK/JNK Signaling, SARS-CoV ATTACHMENT AND ENTRY, TNF-alpha Signaling, Toll like receptors, WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis
Inhibitors 4-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[(5-nitro-2-thiazolyl)thio]-1H-1,2,4-triazol-5-one; anthra[1,9-cd]pyrazol-6(2H)-one
Function Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as proinflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:18307971). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198). Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation (PubMed:21095239). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871). Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons. In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone. Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH (PubMed:20027304, PubMed:17296730, PubMed:16581800). Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteosomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (PubMed:22966201).

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates img/direct-activation.png phosphorylation JUND 0.788
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation PPARG 0.548
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation CDKN1A 0.657
Publications: 2 Organism: Homo Sapiens, In Vitro
Pathways:Acute Myeloid Leukemia, FLT3-ITD in AML
+ up-regulates activity img/direct-activation.png phosphorylation SYT4 0.424
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates img/direct-activation.png phosphorylation H2AX 0.2
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
+ down-regulates img/direct_inhibition.png phosphorylation AIMP1 0.49
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation MAPK8IP1 0.88
Publications: 5 Organism: Chlorocebus Aethiops
Pathways:SAPK/JNK Signaling
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation NFE2 0.421
Publications: 1
+ down-regulates img/direct_inhibition.png phosphorylation CDC25C 0.428
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation IRF3 0.555
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY, Toll like receptors
+ up-regulates activity img/direct-activation.png phosphorylation PXN 0.704
Publications: 1 Organism: Rattus Norvegicus
+ down-regulates img/direct_inhibition.png phosphorylation YWHAZ 0.38
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ down-regulates img/direct_inhibition.png phosphorylation YWHAB 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation SFN 0.349
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TP53 0.79
Publications: 3 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD in AML
+ up-regulates activity img/direct-activation.png phosphorylation TP53 0.79
Publications: 1 Organism: Mus Musculus
Pathways:Acute Myeloid Leukemia, FLT3-ITD in AML
+ down-regulates activity img/direct_inhibition.png phosphorylation RCSD1 0.293
Publications: 3 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation HNRNPK 0.385
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation HNRNPK 0.385
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NR3C1 0.621
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid receptor Signaling
+ up-regulates activity img/direct-activation.png phosphorylation ITCH 0.643
Publications: 5 Organism: Homo Sapiens, Mus Musculus
+ down-regulates activity img/direct_inhibition.png phosphorylation RXRA 0.438
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ down-regulates quantity img/direct_inhibition.png phosphorylation MFN2 0.446
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SIRT1 0.627
Publications: 3 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD in AML
+ up-regulates img/direct-activation.png phosphorylation EIF4ENIF1 0.332
Publications: 6 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation IRS1 0.768
Publications: 5 Organism: Homo Sapiens
Tissue: Muscle, Skeletal Muscle
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation IRS1 0.768
Publications: 1 Organism: Rattus Norvegicus
+ down-regulates activity img/direct_inhibition.png phosphorylation HSF1 0.516
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation STMN1 0.326
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ELK1 0.49
Publications: 1 Organism: Homo Sapiens
Pathways:EGFR Signaling, SAPK/JNK Signaling
+ up-regulates activity img/direct-activation.png phosphorylation ELK1 0.49
Publications: 2 Organism: Homo Sapiens
Pathways:EGFR Signaling, SAPK/JNK Signaling
+ down-regulates img/direct_inhibition.png phosphorylation CTBP1 0.371
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ up-regulates activity img/direct-activation.png phosphorylation ARHGAP8 0.337
Publications: 1
+ down-regulates activity img/direct_inhibition.png phosphorylation SARM1 0.437
Publications: 1
Pathways:Toll like receptors
+ down-regulates activity img/direct_inhibition.png phosphorylation IRS1 0.768
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation BCL2L1 0.772
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network, FLT3-ITD in AML
+ up-regulates activity img/direct-activation.png phosphorylation MYC 0.579
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, EGFR Signaling, FLT3-ITD in AML, WNT Signaling, WNT/FLT3
+ up-regulates activity img/direct-activation.png phosphorylation JUN 0.905
Publications: 2 Organism: Chlorocebus Aethiops
Pathways:Acute Myeloid Leukemia, EGFR Signaling, Glucocorticoid receptor Signaling, SAPK/JNK Signaling, TNF-alpha Signaling, WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis
+ up-regulates activity img/direct-activation.png phosphorylation AP1 0.812
Publications: 2 Organism: Chlorocebus Aethiops
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network, Toll like receptors
+ up-regulates img/direct-activation.png phosphorylation TWIST1 0.316
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation BCL2L11 0.751
Publications: 2 Organism: Mus Musculus, Homo Sapiens
Pathways:COVID-19 Causal Network, SAPK/JNK Signaling
+ up-regulates img/direct-activation.png phosphorylation BCL2 0.559
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network
+ down-regulates img/direct_inhibition.png phosphorylation STAT6 0.366
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ up-regulates activity img/direct-activation.png phosphorylation STAT3 0.591
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, EGFR Signaling, Macrophage polarization
+ down-regulates activity img/direct_inhibition.png phosphorylation ATN1 0.39
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation KRT8 0.384
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation BCL2L11 0.751
Publications: 1 Organism: Mus Musculus
Pathways:COVID-19 Causal Network, SAPK/JNK Signaling
+ up-regulates img/direct-activation.png phosphorylation STK4 0.273
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation BCL2 0.559
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network
+ down-regulates img/direct_inhibition.png phosphorylation PPM1J 0.356
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NR4A1 0.519
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation JUNB 0.721
Publications: 2 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png phosphorylation MAPK8IP1 0.88
Publications: 1 Organism: Chlorocebus Aethiops
Pathways:SAPK/JNK Signaling
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation WDR62 0.577
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation BCL2L11 0.751
Publications: 3 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SAPK/JNK Signaling
+ up-regulates img/direct-activation.png phosphorylation MCL1 0.549
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network
+ up-regulates activity img/direct-activation.png phosphorylation MAPK8 0.736
Publications: 3 Organism: Homo Sapiens, In Vitro
Pathways:COVID-19 Causal Network, EGFR Signaling, Macrophage polarization, SAPK/JNK Signaling, SARS-CoV ATTACHMENT AND ENTRY, TNF-alpha Signaling
+ up-regulates img/direct-activation.png phosphorylation MAPK8 0.683
Publications: 3 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY, TNF-alpha Signaling, Toll like receptors
+ down-regulates img/direct_inhibition.png phosphorylation LAT 0.316
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAPK8IP3 0.713
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SP1 0.693
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ up-regulates activity img/direct-activation.png phosphorylation AKT1 0.441
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates img/direct-activation.png phosphorylation FOXO4 0.596
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation FOXO 0.705
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD in AML
+ down-regulates img/direct_inhibition.png phosphorylation BCL2 0.559
Publications: 3 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network
+ up-regulates img/direct-activation.png phosphorylation ATF2 0.771
Publications: 4 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SAPK/JNK Signaling
+ up-regulates img/direct-activation.png phosphorylation APLP2 0.371
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation APP 0.699
Publications: 2 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation TP53 0.79
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD in AML
+ up-regulates activity img/direct-activation.png phosphorylation STAT1 0.465
Publications: 1 Organism: Mus Musculus
Pathways:EGFR Signaling
+ up-regulates activity img/direct-activation.png phosphorylation BMF 0.676
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png BAX 0.54
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network, SAPK/JNK Signaling, TNF-alpha Signaling
+ down-regulates img/direct_inhibition.png binding MAPK8 0.88
Publications: 4 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ down-regulates img/direct_inhibition.png phosphorylation BAD 0.668
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, COVID-19 Causal Network, FLT3-ITD in AML
+ up-regulates activity img/indirect-activation.png MAPK8 0.485
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY
+ up-regulates img/direct-activation.png binding MAPK8 0.33
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAPK8 0.48
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation OSBP2 0.2
Publications: 1
+ down-regulates img/direct_inhibition.png chemical inhibition MAPK8 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding MAPK8 0.315
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MAPK8 0.643
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD in AML, WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis
+ up-regulates img/direct-activation.png chemical activation MAPK8 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NFATC2 0.74
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates img/indirect-activation.png MAPK8 0.392
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png MAPK8 0.298
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png MAPK8 0.607
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NFATC3 0.832
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png MAPK8 0.432
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png MAPK8 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation MAPK8 0.781
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png chemical activation MAPK8 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation MAPK8 0.7
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ITCH 0.643
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding MAPK8 0.819
Publications: 1 Organism: Homo Sapiens
Pathways:WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis
+ down-regulates img/direct_inhibition.png dephosphorylation MAPK8 0.434
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/indirect_inhibition.png MAPK8 0.621
Publications: 1 Organism: Mus Musculus
Pathways:Glucocorticoid receptor Signaling
+ up-regulates img/direct-activation.png binding MAPK8 0.713
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png MAPK8 0.495
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAPK8 0.302
Publications: 1 Organism: Homo Sapiens
Pathways:WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis
+ down-regulates img/direct_inhibition.png phosphorylation BCL2L11 0.751
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, SAPK/JNK Signaling
+ up-regulates activity img/direct-activation.png relocalization MAPK8 0.577
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png binding MAPK8 0.643
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD in AML, WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis
+ up-regulates img/indirect-activation.png MAPK8 0.262
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
+ up-regulates activity img/direct-activation.png phosphorylation MAPK8 0.393
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition MAPK8 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation PKMYT1 0.341
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAPK9 0.567
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MAPK8 0.432
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png MAPK8 0.326
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates img/direct-activation.png binding MAPK8 0.624
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MAPK8 0.385
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ down-regulates img/direct_inhibition.png dephosphorylation MAPK8 0.706
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png MAPK8 0.643
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD in AML, WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis
+ up-regulates img/indirect-activation.png Actin_cytoskeleton_reorganization 0.7
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation ELK3 0.327
Publications: 1
+ up-regulates img/direct-activation.png phosphorylation LRP6 0.395
Publications: 1 Organism: Homo Sapiens
Pathways:WNT Signaling, WNT/FLT3, WNT Signaling and Myogenesis