Kinase Family DYRK
DYRK ("Dual specificity Tyrosine Regulated Kinase") kinases have an unusual autophosphorylation on tyrosine, but otherwise phosphorylate only on Ser/Thr. The autophosphorylation occurs while still attached to the ribosome, and is an intramolecular reaction . Autophosphorylation occurs on a Y (YxY in DYRK1) in the activation loop which is almost absolutely conserved across all DYRK subfamilies. However, human Dyrk1A is active without this tyrosine phosphorylation, as shown in vitro in phosphatase-treated enzyme, or in mutants in which the substrate Ys are removed .
DYRK consists of the following subfamilies:
HIPK Homeodomain-Interacting Protein Kinase.
DYRKP Originally plant-specific (hence the P) but now found in other lineages.
- Lochhead PA, Sibbet G, Morrice N, and Cleghon V. Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell. 2005 Jun 17;121(6):925-36. DOI:10.1016/j.cell.2005.03.034 |
- Adayev T, Chen-Hwang MC, Murakami N, Lee E, Bolton DC, and Hwang YW. Dual-specificity tyrosine phosphorylation-regulated kinase 1A does not require tyrosine phosphorylation for activity in vitro. Biochemistry. 2007 Jun 26;46(25):7614-24. DOI:10.1021/bi700251n |