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Symbol MAPK8 contributors: shn - updated : 03-07-2017
HGNC name mitogen-activated protein kinase 8
HGNC id 6881
  • tyrosine kinase catalytic domain
  • RIO-like kinase domain
  • conjugated PhosphoP
    interspecies ortholog to MAPK8, Pan troglodytes
    ortholog to mapk8, Danio rerio
    ortholog to Mapk8, Mus musculus
    ortholog to Mapk8, Rattus norvegicus
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • MAP (mitogen activated protein) kinase subfamily
  • CATEGORY enzyme , immunity/defense
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • responding to activation by environmental stress by phosphorylating a number of transcription factor(primarily components of Ap1, C-jun and ATF2)
  • crucial mediator of obesity and insulin resistance
  • required for effector T cell function but not for T cell activation
  • implicated in the immune response that is mediated by the activation and differentiation of CD4 helper T (TH) cells into TH1 and TH2 effector cells
  • JNK1 signaling pathway plays a key role in T cell receptor-initiated TH cell proliferation, apoptosis, and differentiation
  • implicated in the apoptotic response of cells exposed to stress
  • playing a necessary role for epithelial morphogenesis and essential regulator of signal transduction by the EGF receptor in the epidermis
  • promoting abnormal extracellular matrix metabolism in the tissue (in abdominal aortic aneurysm)through suppression of essential enzymes
  • acting with MAPK8 as sensor and downstream effectors of persistent DNA damage in transcribed genes
  • phosphorylating heat shock factor protein 4 (HSF4)
  • acting as a JUN kinase and MAP kinase (serine/threonine kinase)
  • involved in the activation of pro-apoptotic gene products
  • playong a role in cell mobility
  • involved in the negative regulation of apoptosis
  • involved in UV radiation induced apoptosis
  • playing a key role in T cell proliferation, apoptosis and differentiation
  • its activity is required for protection of liver from hepatic steatosis
  • required for IL-3-mediated cell survival through phosphorylation and inactivation of the proapoptotic Bcl-2 family protein BAD (
  • JNK pathway is critically involved in diabetes
  • play a role in the developing nervous system and T-cell-mediated immunity
  • necessary for epithelial morphogenesis and is an essential regulator of signal transduction by the EGF receptor in the epidermis
  • may play an important part in maintaining microtubule stability and efficient neurite elongation
  • both MAPK8 and MAPK9, have cytotoxic potential, however MAPK9 is the primary signal transducer
  • implicated in diet-induced obesity
  • role of neuronal and pituitary MAPK8 as a regulator of hypothalamic and peripheral insulin sensitivity as well as somatic growth
  • critical role in pituitary control of thyroid function
  • plays a key role in Ras-induced tumorigenesis
  • has dual roles in the regulation of SIRT1 activity; it induces and then decreases the SIRT1 activity through the phosphorylation-mediated processes
  • MAPK10 mediates potentially its effects mainly at the transcriptional level, while MAPK8 or MAPK9 appear to mediate their pro-apoptotic effect in the cytoplasm
  • is essential for coordination of NTN1/DCC and NTN1/DSCAM signaling and plays an important role in Netrin-1-induced axon outgrowth and pathfinding
  • is required for commissural axon projection and pathfinding in the developing spinal cord
  • MAPK8 increases YAP1 activity by promoting the binding of AJUBA family proteins to LATS1
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    cell migration & motility
    PHYSIOLOGICAL PROCESS immunity/defense
    signaling signal transduction
  • response to UV and stress
  • MAPK8-SIRT1 pathway provides a new molecular mechanism for the pathogenesis of hepatic steatosis in obesity
  • MAP2K7-MAPK8 signaling plays an important regulatory role in neural development and MAP2K7-MAPK8 signaling pathway plays important roles in regulating circadian rhythms and neuronal maintenance in the adult nervous system
  • a component
    small molecule cofactor, nucleotide,
  • Mg2+
  • ATP
  • protein
  • Rho GTPase activating protein 1 (ARHGAP1)
  • four scaffolding proteins: MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4
  • ERK-2 and Elk1 (
  • tumor protein p53, TP53 (
  • mitogen-activated protein kinase kinase kinase 1, MEKK1 (
  • mitogen-activated protein kinase 5, MKP5 (
  • Jun N-terminal protein kinase (JNK)/stress-activated protein kinase-associated protein 1, JSAP1 (
  • c-Myc (
  • COP9 signalosome (
  • MEK kinase 2 and c-Jun N-terminal kinase (JNK) kinase 2 (
  • insulin receptor substrate 1, IRS1 (
  • heat shock transcription factor 1, HSF1 (
  • Mitogen-activated protein (MAP) kinase phosphatase 1, MKP-1/CL100 (
  • Glutathione S-transferase P1-1, GSTP1-1 (
  • v-crk sarcoma virus CT10 oncogene homolog (avian), CRK (
  • Jun dimerization protein 2, JDP2 (
  • Protein kinase D, PKD (
  • I kappa B kinase complex-associated protein, IKAP (
  • SH3-domain binding protein 5, SH3BP5 (
  • c-Jun NH2-terminal kinase-associated leucine zipper protein, JLP (
  • SH3-domain binding protein 5, SH3BP5 (
  • cyclin-dependent kinase inhibitor 2A, CDKN2A
  • JNK1/MAPK8-associated membrane protein, JAMP (
  • histone deacetylase-related protein, HDRP (
  • mitogen-activated protein kinase 8 interacting protein 2 (MAPK8IP2)
  • synuclein, gamma (breast cancer-specific protein 1) (SNCG)
  • mitogen-activated protein kinase 3 (MAPK3)
  • Protein kinase D (PKD)
  • IFNA1-induced the expression of IFIT3 and STAT1 in THP-1 cells, and this process was significantly antagonized by the specific inhibitors of both PRKCD and MAPK8
  • MAPK8 target gene, is myosin phosphatase-Rho interacting protein (MPRIP)
  • mitogen-activated protein kinase 9 (MAPK9 also known as JNK2)
  • sirtuin 1, SIRT1 (
  • MAPK8 activation is required for GNA12-induced invasion of breast cancer cells and MAPK8 is downstream of ROCK1 on this pathway
  • mediates the up-regulation of proinflammatory genes in lipin-2-deficient macrophages
  • interactions of NRL with c-Jun N-terminal kinase 1 (MAPK8) and HIV Tat-interacting protein 60 (KAT5)
  • mediates the expression of CTGF and corneal scarring in corneal wound healing
  • RAD18 phosphorylation by MAPK8 represents a novel mechanism for promoting translesion synthesis (TLS) and DNA damage tolerance
  • stimulation of nTregs through TNFRSF18 initiates a signaling cascade that involves MAP2K7, MAPK8 phosphorylation, JUN activation, and the activation of NFKB1
  • MAPK8 binds and phosphorylates paxillin to regulate Schwann cell migration
  • MAPK8 serves as a crucial component in mediating glucose-responsive upregulation of ADAR2 expression in pancreatic beta-cells
  • plays an important role in NTN1-mediated axon guidance in the developing nervous system
  • is important in the coordination of DCC and DSCAM in NTN1-mediated attractive signaling
  • AJUBA is required for MAPK8-mediated activation of YAP1 and AJUBA contributed to wing regeneration after wounding and to tumor growth
  • MUC1 binds to and activates MAPK8
  • ER stress triggers an interaction of MAPK8 with mitochondrial SH3BP5, which leads to impaired respiration and increased mitochondrial reactive oxygen species, sustaining MAPK8 activation culminating in apoptosis
  • TGFB1I1 serves as a novel scaffold protein that specifically activates MAP2K4/MAPK8 pathway, thereby leading to the induction and activation of MMP in smooth muscle cells and subsequent abdominal aortic aneurysm (AAA) formation
  • WDR62 specifically recruits MAPK8, but not MAPK9, to the spindle pole
  • IFIT3 showed binding to MAPK8 and STAT1, the latter being an important inducer of IFIT3 expression
  • increasing TRAF5 ameliorates nonalcoholic fatty liver by blocking MAPK8 activity
  • MAP2K7, which selectively phosphorylates MAPK8, is a SENP3 substrate and SENP3-mediated deSUMOylation of MAP2K7 may favor its binding to MAPK8
  • cell & other
    activated by PIAS1 (protein inhibitor of activated STAT1)
    TNF (TNF-alpha) for TNF-induced preferential release of DIABLO
    threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7
    mitogen-activated protein kinase kinase 7 (MKK7)
    NLR family, apoptosis inhibitory protein (NAIP) and baculoviral IAP repeat-containing 7 (BIRC7 also known as ML-IAP)
    TGF-beta in a SMAD-independent manner
    a high-fat diet and triggers development of insulin resistance
    COP9 (
    JKAP (
    I kappa B kinase complex-associated protein, IKAP (
    inhibited by dual specificity phosphatases (DUSP), such as DU
    Glutathione S-transferase P1-1, GSTP1-1 (
    repressed by cyclin-dependent kinase inhibitor 2A, CDKN2A
    Other regulation of its activity by NF-kappaB during TGF-beta1 signaling
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    in obesity
    constitutional       loss of function
    deficiency in the nervous system is sufficient to account for the role of MAPK8 in the regulation of high-fat diet-induced weight gain
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • JNK-related therapeutic strategies for RP1 diseases
  • SystemTypeDisorderPubmed
    a potential new therapy for diabetes using cell-permeable JNK-inhibitory peptide
    therapeutic target in abdominal aortic aneurysm
    JNK activity observed in wild-type activated TH cells was severely reduced in TH cells from Jnk1-/- mice
  • MAPK8 deficient mice display a progressive loss of axonal and dendritic microtubules and MAP1B and MAP2 are hypophosphorylated in MAPK8/ brains compromising their ability to bind to microtubules and promote their assembly and stability
  • Mice lacking both of the ubiquitously expressed isoforms JNK1 and -2 die during midgestation with neural tube closure defects and brain abnormalities
  • JNK-deficient mice exhibit delayed epithelial development in the epidermis, intestines, lungs, an eyelid closure defect associated with markedly reduced epidermal growth factor (EGF) receptor function, and loss of expression of the ligand EGF
  • genetic loss of the MAPK, c-Jun N-terminal kinase 1 in a mouse model of multiple sclerosis, enhances IL-10 production, rendering innate myeloid cells unresponsive to certain microbes and less capable of generating IL-17-roducing, encephalitogenic T cells