The DYRK family includes several dual-specificity tyrosine-phosphorylated and regulated kinases capable of phosphorylating proteins at both Tyr and Ser/Thr residues. The DYRK family was identified based on homology to the yeast Yak1 and the Drosophila minibrain (mnb) kinases. Seven mammalian isoforms have been discovered, including DYRK1A, DYRK1B, DYRK1C, DYRK2, DYRK3, DYRK4, and DYRK4B. Differences in substrate specificity, expression, and subcellular localization are seen across the DYRK family. All DYRK proteins have a Tyr-X-Tyr motif in the catalytic domain activation loop, phosphorylation of the second Tyr residue (e.g. Tyr312 of DYRK1A) is necessary for kinase activity. DYRKs typically autophosphorylate the Tyr residue within their activation loop, but phosphorylate substrates at Ser and Thr residues. DYRK2 is thought to play a role in checkpoint control of the cell cycle. DYRK2 can phosphorylate p53 at Ser46 following cellular damage, leading to activation of the apoptotic response. Research studies have demonstrated overexpression of DYRK2 in esophageal and lung adenocarcinomas, with DYRK2 expression levels acting as a potential predictor of chemotherapy treatment outcomes in non-small cell lung cancer.
