Dual specificity tyrosine-phosphorylation-regulated kinase (DYRK)

Dual specificity tyrosine-phosphorylation-regulated kinases (DYRKs) are a conserved family of protein kinases characterized by their ability to autophosphorylate on tyrosine residues while phosphorylating substrate proteins on serine/threonine residues. The human DYRK family includes DYRK1A, DYRK1B, DYRK2, DYRK3, and DYRK4, grouped within the CMGC kinase family. DYRKs play fundamental roles in cell cycle regulation, cell proliferation, apoptosis, DNA damage repair, neuronal development, synaptic function, and mRNA processing. Abnormal DYRK expression or activity contributes to the pathogenesis of numerous diseases, including multiple cancers (such as breast cancer, prostate cancer, multiple myeloma, and leukemia), neurodegenerative disorders (notably Alzheimer's and Parkinson's disease), developmental syndromes (e.g., Down syndrome), diabetes, and viral infections. DYRK2, for instance, regulates the proteasome and cytoskeleton, and its inhibition impairs cancer cell proliferation and tumor growth, supporting its candidacy as a novel therapeutic target in oncology. Multiple selective and nonselective DYRK inhibitors are under investigation, though clinical data remain limited. Selectivity, impact on nonmalignant cells, and biomarker development are current therapeutic challenges.

Other names

DYRK familyDual-specificity tyrosine-(Y)-phosphorylation-regulated kinaseDYRK1ADYRK1BDYRK2DYRK3DYRK4

Inhibition of kinase activity (blocking phosphorylation of Ser/Thr/Tyr residues on substrates); Partial inhibition of 26S proteasome function (DYRK2 specific); Modulation of cell cycle progression and apoptosis in cancer; Reduction of pathological hyperphosphorylation in neurological disease