Microtubule affinity-regulating kinase 2 (MARK2) (MARK2)

Microtubule affinity-regulating kinase 2 (MARK2), also known as Par1b, is a serine/threonine kinase that plays a fundamental role in establishing and maintaining cell polarity across various tissues (UniProt P54829). It acts by phosphorylating microtubule-associated proteins (MAPs), including Tau, MAP2, and MAP4, at specific KXGS motifs, which causes these proteins to detach from microtubules and leads to increased microtubule dynamics (PubMed: 9244301). This function is essential for neuronal development, particularly in axon specification and dendrite formation, as well as for maintaining the apical-basal polarity of epithelial cells. In pathological contexts, MARK2 is strongly associated with Alzheimer's disease, where it is one of the primary kinases responsible for the initial phosphorylation of Tau that precedes the formation of neurofibrillary tangles (PubMed: 17519550). Furthermore, MARK2 has been implicated in cancer progression due to its role in cell cycle regulation and the maintenance of cell structure, and it also influences metabolic pathways such as insulin signaling (PubMed: 23584055). Although specific MARK2 inhibitors are currently in the experimental stage, they represent a promising therapeutic strategy for mitigating Tau-mediated neurodegeneration and certain oncogenic processes.

Other names

Par1bPAR-1bELKL motif kinase 1EMK-1Serine/threonine-protein kinase MARK2

Inhibition of serine/threonine kinase activity to modulate microtubule stability and prevent hyperphosphorylation of microtubule-associated proteins (MAPs).