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mitogen-activated protein kinase 10 (stress-activated protein kinase JNK3, c-Jun N-terminal kinase 3, p49 3F12 MAP kinase, MAPK10, JNK3, JNK3A, PRKM10)

Function: - responds to activation by environmental stress & pro- inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 including c-Jun & ATF2 & thus regulates AP-1 transcriptional activity required for stress-induced neuronal apoptosis & the pathogenesis of glutamate excitotoxicity (putative) - binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 & SPAG9/MAPK8IP4/JIP-4 - these proteins also bind other components of the JNK signaling pathway - interacts with HDAC9 - activated by Thr & Tyr phosphorylation by two dual specificity kinases, MAP2K4 & MAP2K7 - MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change & a large increase in Vmax - MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax inhibited by dual specificity phosphatases, such as DUSP1 inhibited by HDAC9 - dually phosphorylated on Thr-221 & Tyr-223, which activates the enzyme - weakly autophosphorylated on Thr & Tyr in vitro - phosphorylates ELK-1 - inhibited by map kinase phosphatase MKP-1 - found in complex with beta-arrestin 2, ASK1 & MKK4 Cofactor: Mg+2 Structure: - TXY motif contains the Thr & Tyr whose phosphorylation activates the MAP kinases - belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family. MAP kinase subfamily - contains 1 protein kinase domain - mass=44070; method=Electrospray; Range=1-464 [4] Compartment: cytoplasm Alternative splicing: named isoforms=2, alpha-2, alpha-1 Expression: - specific to a subset of neurons in the nervous system - present in the hippocampus & areas, cerebellum, striatum, brain stem, & weakly in the spinal cord - very weak expression in testis & kidney Pathology: 1) chromosomal translocation t(Y;4)(q11.2;q21) involving MAPK10 is a cause of epileptic encephalopathy Lennox-Gastaut type - causes MAPK10 truncation 2) colocalizes with Alz-50 antigen in hippocampal sections of brains from Alzheimer's disease patients

Interactions

molecular events

Related

gene

General

c-jun NH2 terminal kinase, jun kinase (JNK) or stress-activated protein kinase (SAPK)

Properties

SIZE: entity length = 464 aa MW = 53 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: kinase domain SITE: 64-359 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 70-78 ATP-binding site NAME: ATP-binding site SITE: 93-93 aspartate residue {D189} TXY {221-223} Thr phosphorylation site {T221} Tyr phosphorylation site {Y223}

References

  1. Mohit et al Neuron 14:67 1995
  2. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/JNK3ID427.html
  3. UniProt :accession P53779
  4. Mass Spec PMID: 10715136

Databases & Figures

OMIM correlations UniProt P53779 Pfam PF00069 Entrez Gene 5602 KEGG correlations ENZYME 2.7.11.24 MAP kinase pathways