Dual-specificity tyrosine-phosphorylation-regulated kinase 1-4 (DYRK1-4)

Dual-specificity tyrosine-phosphorylation-regulated kinases (DYRK1-4) are a family of evolutionarily conserved protein kinases belonging to the CMGC group, which includes members DYRK1A, DYRK1B, DYRK2, DYRK3, and DYRK4. These kinases are unique in their ability to autophosphorylate on tyrosine residues for activation while phosphorylating substrates on serine and threonine residues. They play pivotal roles in a wide array of cellular processes, including cell cycle control, neuronal development, and intracellular signaling. DYRK1A is particularly well-studied for its involvement in the cognitive deficits of Down syndrome and the pathogenesis of Alzheimer's disease, where it contributes to tau hyperphosphorylation. Other family members, such as DYRK1B, are implicated in cancer cell survival, chemoresistance, and metabolic syndrome. Therapeutic strategies focusing on DYRK1-4 involve the development of small-molecule inhibitors to modulate their activity in neurodegenerative diseases, diabetes, and various malignancies.

Other names

DYRK familyDual-specificity tyrosine-regulated kinase familyMirk (for DYRK1B)REDK (for DYRK3)Minibrain-related kinase

ATP-competitive inhibition of kinase activity, preventing the phosphorylation of downstream substrates such as Tau, NFAT, and Cyclin D1.