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Target intelligence / Profile preview
Mixed lineage kinase domain-like protein S441 kinase (MLKL S441 kinase)
- Target
- MLKL S441 kinase
- Molecular classification
- Enzyme, Kinase, Serine/threonine-protein kinase
01
Overview
- Other names
- Unknown S441 kinaseMyelin breakdown-triggering kinaseSchwann cell-activated MLKL kinase
02
Mechanism of action
The unknown kinase phosphorylates MLKL at Ser441 in Schwann cells following nerve injury. This phosphorylation induces a conformational change that allows MLKL to insert into the myelin sheath lipid bilayer (specifically binding to sulfatide), leading to myelin decompaction and breakdown [25, 41, 43].
03
Biological functions
Myelin breakdownDemyelinationNerve injury responseSchwann cell signaling
04
Disease associations
Charcot-Marie-Tooth diseaseCMT4B2-like peripheral neuropathyDiabetic neuropathyMultiple sclerosisAxonal degeneration
05
Safety considerations
Potential interference with normal myelin remodelingRisk of affecting necroptosis pathways in other tissuesChallenges in achieving Schwann cell-specific delivery
06
Interacting drugs
Necrostatin-1 (indirectly via RIPK1)
2 more in the full profile.
07
Biomarkers
Phospho-MLKL (S441)Myelin basic protein (MBP) degradation productsNerve conduction velocity (NCV)
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