Mapk8 (rat, P49185) - manual literature research

No deep-research API provider was available for this session. This file records the
literature work done by hand from the cached publications in publications/ and the
UniProt record. Every statement carries inline provenance.

Identity and family

• Rat Mapk8 encodes JNK1 / SAPK gamma, a 411-aa member of the CMGC Ser/Thr kinase group,
  MAP kinase subfamily [file:rat/Mapk8/Mapk8-uniprot.txt "Belongs to the protein kinase
  superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily."].
• Kinase domain 26-321, catalytic Asp151 proton acceptor, activation-loop TXY motif 183-185
  [file:rat/Mapk8/Mapk8-uniprot.txt "The TXY motif contains the threonine and tyrosine
  residues whose phosphorylation activates the MAP kinases."].
• InterPro IPR008351 (MAPK_JNK) and PANTHER PTHR24055 place it in the JNK clade.

Activation and regulation

• Activated by dual phosphorylation of Thr183/Tyr185 by MAP2K4 and MAP2K7 (by similarity to
  human P45983) [file:rat/Mapk8/Mapk8-uniprot.txt "Dually phosphorylated on Thr-183 and
  Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme."].
• In rat cerebellar granule neurons deprived of potassium, MKK7 (not MKK4) is the upstream
  activator of the JNK pathway PMID:11849756.
• Inhibited by S-nitrosylation of Cys116 after IFN-gamma-induced NO production; rat alveolar
  macrophages were among the cells tested PMID:11121042.
• Activated in perfused rat heart by H2O2 and ischaemia/reperfusion PMID:9516415; by IL-1 beta in rat UMR-106 osteoblastic cells
  PMID:9513050; by TNF-alpha, HGF and
  hyperosmotic glucose in primary rat hepatocytes PMID:9487126.

Substrates and direct functions (rat or rat-cell experiments)

• c-Jun Ser63 phosphorylation downstream of SEK/JNK1 in rat hepatocytes, required for agonist
  stimulated DNA synthesis PMID:9487126.
• SCG10/stathmin-2 Ser62/Ser73 phosphorylation; JNK1 controls microtubule dynamics and
  axodendritic length in rat cortical neurons PMID:16618812. Active JNK and SCG10 co-fractionate in vesicular (P2) membranes
  PMID:16618812.
• SCG10 phosphorylation by cytoplasmic JNK1 restrains exit from the multipolar stage and radial
  migration PMID:21297631.
• Paxillin Ser178 phosphorylation, needed for rapid migration of rat NBT-II bladder carcinoma
  cells PMID:12853963.
• Synaptotagmin-4 Ser135 phosphorylation (PC12 cells, rat hippocampal neurons), which releases
  Syt4 from KIF1A and captures dense core vesicles at synapses PMID:29166604;
  in PC12 cells PMID:18046461.
• AMPA receptor GluR2L Thr912 and GluR4 Thr855 phosphorylation; JNK1 co-precipitates with these
  subunits from rat brain PMID:18188153.

Cell-survival and apoptosis phenotypes (context dependent)

• Pro-apoptotic: antisense JNK1 blocked reoxygenation-induced apoptosis of rat cardiac
  myocytes PMID:11259632; beta-amyloid-induced p53 stabilisation and apoptosis of cortical
  neurons PMID:12534344; tamoxifen-induced apoptosis of rat glioma cells PMID:14997384.
• Anti-apoptotic: JNK1 shRNA increased palmitate/high-glucose-induced apoptosis of INS-1 beta
  cells PMID:24475223;
  SP600125 increased apoptosis during simulated ischaemia/reperfusion of neonatal
  cardiomyocytes PMID:15309413.
• These opposing outcomes are cell-type and stimulus specific; they are downstream
  consequences of the kinase acting on different substrates, not distinct activities.

Metabolic stress

• Palmitate activates JNK in rat H4IIEC3 hepatocytes via mitochondrial ROS, and the pan-JNK
  inhibitor SP600125 restores insulin-stimulated Akt/GSK-3 phosphorylation PMID:19332540. The study did not distinguish JNK1 from JNK2 (pharmacological
  inhibition only), so it does not by itself attribute the effect to Mapk8.
• Oxidative stress in rat islets suppresses insulin gene expression through JNK, with reduced
  PDX-1 DNA binding PMID:12011047.

Localisation

• Cytoplasm (cortical neurons, predominantly cytoplasmic and on Golgi/endosomal membranes)
  and nucleus [file:rat/Mapk8/Mapk8-uniprot.txt "In the cortical neurons, predominantly
  cytoplasmic and associated with the Golgi apparatus and endosomal fraction"].
• Adult rat CNS: cytoplasm, dendrites and axons of neurons PMID:9714150.
• Phosphorylated JNK concentrated at synapses after neuronal activity PMID:29166604.