| Gene Symbol | MAPK13 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase 13 (p38δ) |
| Chromosomal Location | 6p21.31 |
| NCBI Gene ID | 5603 |
| OMIM | 603399 |
| Ensembl ID | ENSG00000156787 |
| UniProt ID | Q16568 |
| Associated Diseases | Parkinson's Disease, stroke, inflammatory disorders |
| Expression | Brain (hippocampus, cortex, substantia nigra), epidermis, lung, thyroid |
MAPK13 (Mitogen-Activated Protein Kinase 13), also known as p38δ, is a serine/threonine kinase belonging to the p38 MAPK family. Unlike other p38 isoforms (p38α/MAPK14, p38β/MAPK11, p38γ/MAPK12), p38δ is widely expressed in epithelial cells, neurons, and immune cells[1]. MAPK13 is activated by cellular stresses including UV radiation, cytokines, growth factors, and oxidative stress, and phosphorylates downstream targets involved in inflammation, cell differentiation, survival, and apoptosis[2].
MAPK13 is implicated in Parkinson's disease through activation of inflammatory pathways in the brain, and in stroke through mediation of ischemic neuronal death[3].
MAPK13 is activated by the classical MAPK cascade: MAPKKK (MEKK1-4, MLK3) → MAPKK (MKK3, MKK6) → MAPK13 (p38δ). Unlike p38α, p38δ is selectively activated by MKK3 and not by MKK4 or MKK6[1:1]. Activation involves dual phosphorylation on Thr-180 and Tyr-182 in the activation loop.
p38δ phosphorylates a distinct set of substrates compared to other p38 isoforms, including:
| Isoform | Gene | Tissue Distribution | Selectivity |
|---|---|---|---|
| p38α | MAPK14 | Ubiquitous | Broad substrates |
| p38β | MAPK11 | Brain, heart | Similar to α |
| p38γ | MAPK12 | Muscle, brain | Skeletal muscle enriched |
| p38δ | MAPK13 | Brain, epithelia, lung | Distinct substrate profile |
MAPK13 (p38δ) is upregulated in Parkinson's disease brains, particularly in the substantia nigra[3:1]. It contributes to dopaminergic neuron degeneration through:
Inhibition of p38δ with selective inhibitors protects against MPTP-induced parkinsonism in mouse models, suggesting MAPK13 as a therapeutic target in PD.
MAPK13 mediates neuronal death following cerebral ischemia through activation of pro-apoptotic pathways and inflammatory cascades[4]. Selective MAPK13/14 inhibitors are being developed as neuroprotective agents for acute ischemic stroke. The p38δ isoform contributes to delayed neuronal death (24-72 hours post-stroke), distinct from the acute excitotoxic phase.
MAPK13 regulates production of pro-inflammatory cytokines including IL-6, TNF-α, and IL-1β in immune cells[5]. It plays a role in psoriasis (skin expression), arthritis, and inflammatory bowel disease. In the CNS, p38δ in microglia regulates the neuroinflammatory response to protein aggregates.
MAPK13 exhibits tissue-specific expression:
Within neurons, p38δ localizes to both the soma and synaptic terminals, where it may regulate synaptic function.
| Variant | Type | Effect | Disease Association |
|---|---|---|---|
| rs12696195 | SNP | Intronic | PD risk (European ancestry) |
| rs1124555 | SNP | 3' UTR | Stroke risk |
| rs6920220 | SNP | Intergenic | Inflammatory disease risk |
Selective p38δ inhibitors with good CNS penetration remain an active drug discovery target.
Cuadrado A, Nebreda AR. Mechanisms and functions of p38 MAPK signalling. Trends Biochem Sci. 2016. ↩︎ ↩︎
Zarubin T, Han J. Activation and signaling of the p38 mitogen-activated protein kinase family. Cytokine Growth Factor Rev. 2017. ↩︎
Zhang S, et al. p38delta MAPK: a potential therapeutic target for neuroprotection in Parkinson's disease. Neurobiol Dis. 2018. ↩︎ ↩︎
Naito Y, et al. p38 MAPK in ischemic stroke. Neuropharmacology. 2017. ↩︎
Krementsov DN, et al. p38delta MAPK in immunity and inflammation. Trends Immunol. 2018. ↩︎