Tau-protein kinase refers to any kinase enzyme that catalyzes the transfer of a phosphate group from ATP to the tau protein (also known as microtubule-associated protein tau, MAPT). Phosphorylation of tau regulates its ability to bind microtubules and modulates neuronal cytoskeletal stability.
Classification
- Enzyme Commission (EC) number: 2.7.11.23 (designated “tau‑protein kinase”).
- Belongs to the protein kinase superfamily, specifically serine/threonine kinases that target residues on the tau protein.
Physiological role
- Basal phosphorylation of tau by tau‑protein kinases controls microtubule dynamics, axonal transport, and neuronal signaling.
- Kinases such as glycogen synthase kinase‑3β (GSK‑3β), cyclin‑dependent kinase 5 (CDK5), microtubule‑affinity‑regulating kinase (MARK) family members, protein kinase A (PKA), and protein kinase C (PKC) are commonly identified as tau‑protein kinases in the central nervous system.
Pathological relevance
- Hyperphosphorylation of tau by over‑active tau‑protein kinases contributes to the formation of neurofibrillary tangles, a hallmark of Alzheimer’s disease and other tauopathies.
- Dysregulation of GSK‑3β, CDK5 (often via its activator p35/p25), and MARKs has been implicated in abnormal tau phosphorylation patterns observed in neurodegenerative conditions.
Regulation
- Tau‑protein kinase activity is modulated by upstream signaling pathways (e.g., insulin/PI3K‑AKT for GSK‑3β, calcium/calmodulin for CDK5).
- Post‑translational modifications of the kinases themselves (phosphorylation, proteolysis) and interactions with scaffolding proteins influence substrate specificity toward tau.
Research and therapeutic context
- Inhibitors targeting specific tau‑protein kinases (e.g., selective GSK‑3β inhibitors) are under investigation as potential disease‑modifying agents for Alzheimer’s disease and related disorders.
- Experimental models often employ knock‑down or over‑expression of individual tau‑protein kinases to assess their contribution to tau pathology.
Note
The term “tau‑protein kinase” is a functional descriptor rather than a single, uniquely named enzyme; it encompasses multiple serine/threonine kinases that phosphorylate the tau protein.
