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 162
Pathways EGFR, Tol like receptors, SAPK/JNK Signaling, WNT Signaling, WNT Signaling and Myogenesis, TNF alpha, Macrophage polarization, Glucocorticoid Receptor
Inhibitors 1,9-Pyrazoloanthrone; 883065-90-5
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. Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. 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. 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. Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy. 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. 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).

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates img/direct-activation.png phosphorylation JUND 0.13
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PPARG 0.10
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ up-regulates img/direct-activation.png phosphorylation CDKN1A 0.26
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation AIMP1 0.11
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation H2AFX 0.11
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
+ img/unknown.png phosphorylation MAPK8IP1 0.35
Publications: 5 Organism: Chlorocebus Aethiops
Pathways:SAPK/JNK Signaling
+ down-regulates img/direct_inhibition.png phosphorylation CDC25C 0.10
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation IRF3 0.13
Publications: 1 Organism: Homo Sapiens
Pathways:Tol like receptors
+ up-regulates activity img/direct-activation.png phosphorylation PXN
Publications: 1 Organism: Rattus Norvegicus
+ down-regulates img/direct_inhibition.png phosphorylation YWHAZ 0.12
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ down-regulates img/direct_inhibition.png phosphorylation SFN 0.11
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation YWHAB 0.11
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TP53 0.13
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation TP53 0.13
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation HNRNPK 0.13
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation HNRNPK 0.13
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NR3C1 0.11
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid Receptor
+ up-regulates activity img/direct-activation.png phosphorylation ITCH
Publications: 5 Organism: Homo Sapiens, Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation RXRA 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SIRT1 0.12
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation H3F3A 0.06
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation EIF4ENIF1 0.09
Publications: 6 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation IRS1 0.26
Publications: 9 Organism: Homo Sapiens
Tissue: Muscle, Skeletal Muscle
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation IRS1 0.26
Publications: 1 Organism: Rattus Norvegicus
+ down-regulates activity img/direct_inhibition.png phosphorylation HSF1 0.11
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation STMN1 0.10
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ELK1 0.27
Publications: 1 Organism: Homo Sapiens
Pathways:EGFR, SAPK/JNK Signaling
+ up-regulates activity img/direct-activation.png phosphorylation ELK1 0.27
Publications: 2 Organism: Homo Sapiens
Pathways:EGFR, SAPK/JNK Signaling
+ down-regulates img/direct_inhibition.png phosphorylation CTBP1 0.10
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MYC 0.11
Publications: 2 Organism: Homo Sapiens
Pathways:EGFR, WNT Signaling
+ down-regulates img/direct_inhibition.png phosphorylation BCL2L1 0.19
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation JUN 0.91
Publications: 2 Organism: Chlorocebus Aethiops
Pathways:EGFR, Glucocorticoid Receptor, SAPK/JNK Signaling, TNF alpha, WNT Signaling, WNT Signaling and Myogenesis
+ up-regulates activity img/direct-activation.png phosphorylation AP1
Publications: 2 Organism: Chlorocebus Aethiops
+ up-regulates img/direct-activation.png phosphorylation TWIST1 0.03
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation BCL2L11 0.19
Publications: 2 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates activity img/direct-activation.png phosphorylation BCL2L11 0.19
Publications: 2 Organism: Mus Musculus
Pathways:SAPK/JNK Signaling
+ up-regulates img/direct-activation.png phosphorylation BCL2 0.29
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation STAT6 0.11
Publications: 1 Organism: Homo Sapiens
Pathways:Macrophage polarization
+ up-regulates activity img/direct-activation.png phosphorylation STAT3 0.25
Publications: 1 Organism: Homo Sapiens
Pathways:EGFR, Macrophage polarization
+ down-regulates activity img/direct_inhibition.png phosphorylation ATN1 0.04
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ up-regulates img/direct-activation.png phosphorylation KRT8
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STK4 0.15
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation BCL2
Publications: 5 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PPM1J 0.05
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NR4A1 0.13
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation JUNB 0.13
Publications: 2 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png phosphorylation MAPK8IP1 0.35
Publications: 2 Organism: Homo Sapiens, Chlorocebus Aethiops
Pathways:SAPK/JNK Signaling
+ up-regulates img/direct-activation.png phosphorylation BCL2L11 0.19
Publications: 3 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates img/direct-activation.png phosphorylation MCL1 0.14
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAPK8
Publications: 3 Organism: Homo Sapiens, In Vitro
Pathways:EGFR, Macrophage polarization, SAPK/JNK Signaling, TNF alpha
+ up-regulates img/direct-activation.png phosphorylation MAPK8 0.57
Publications: 3 Organism: Homo Sapiens
Pathways:TNF alpha, Tol like receptors
+ down-regulates img/direct_inhibition.png phosphorylation LAT
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAPK8IP3 0.13
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation SP1 0.12
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation AKT1
Publications: 1 Organism: Rattus Norvegicus
+ up-regulates img/direct-activation.png phosphorylation FOXO4 0.03
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation FOXO
Publications: 2 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation CDKN1A
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation ATF2 0.45
Publications: 4 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates img/direct-activation.png phosphorylation APLP2 0.09
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation APP
Publications: 2 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation TP53 0.13
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation STAT1 0.20
Publications: 1 Organism: Mus Musculus
Pathways:EGFR
+ up-regulates img/direct-activation.png binding MAPK8 0.08
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates img/direct-activation.png binding MAPK8 0.03
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MAPK8 0.13
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAPK8 0.17
Publications: 1 Organism: Homo Sapiens
Pathways:WNT Signaling, WNT Signaling and Myogenesis
+ up-regulates img/direct-activation.png phosphorylation LRP6 0.08
Publications: 1 Organism: Homo Sapiens
Pathways:WNT Signaling, WNT Signaling and Myogenesis
+ up-regulates img/direct-activation.png binding MAPK8 0.10
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png unknown MAPK8 0.28
Publications: 1 Organism: Homo Sapiens
Pathways:WNT Signaling, WNT Signaling and Myogenesis
+ up-regulates img/indirect-activation.png unknown MAPK8 0.05
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
+ up-regulates img/direct-activation.png binding MAPK8 0.28
Publications: 1 Organism: Homo Sapiens
Pathways:WNT Signaling, WNT Signaling and Myogenesis
+ up-regulates activity img/direct-activation.png binding MAPK8 0.28
Publications: 1 Organism: Homo Sapiens
Pathways:WNT Signaling, WNT Signaling and Myogenesis
+ up-regulates img/direct-activation.png phosphorylation MAPK9 0.87
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png chemical activation MAPK8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NFATC3 0.07
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation NFATC2 0.06
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates img/direct-activation.png chemical activation MAPK8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition MAPK8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ITCH 0.12
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MAPK8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation PKMYT1 0.12
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding MAPK8 0.35
Publications: 4 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates img/indirect-activation.png unknown MAPK8
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates img/indirect-activation.png unknown MAPK8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation BAD 0.18
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation ELK3
Publications: 1
+ up-regulates activity img/direct-activation.png phosphorylation BMF
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/indirect_inhibition.png binding MAPK8
Publications: 1 Organism: Mus Musculus
Pathways:Glucocorticoid Receptor
+ down-regulates img/direct_inhibition.png dephosphorylation MAPK8 0.06
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MAPK8 0.03
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition MAPK8
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ down-regulates img/indirect_inhibition.png unknown MAPK8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png unknown MAPK8 0.08
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png unknown BAX
Publications: 1 Organism: Homo Sapiens
Pathways:SAPK/JNK Signaling
+ up-regulates img/indirect-activation.png unknown MAPK8 0.02
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation MAPK8 0.11
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png unknown MAPK8 0.19
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png unknown MAPK8 0.12
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MAPK8 0.31
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation MAPK8 0.16
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation MAPK8 0.41
Publications: 1 Organism: Homo Sapiens