Research ArticleKinases

Characterization of a Domain That Transiently Converts Class 2 DYRKs into Intramolecular Tyrosine Kinases

Sci. Signal.  02 Mar 2010:
Vol. 3, Issue 111, pp. ra16
DOI: 10.1126/scisignal.2000579

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Many protein kinases must undergo phosphorylation of particular amino acid residues in their activation loops to become activated. Such reactions can occur in an intermolecular manner, either by another kinase or by another molecule of the same kinase, or through an intramolecular mechanism. The dual-specificity tyrosine phosphorylation–regulated kinases (DYRKs) represent one of two families of kinases whose activation loop tyrosine residue is phosphorylated intramolecularly. However, DYRKs phosphorylate their substrates on serine or threonine residues, so it is unclear how a single kinase domain can have both activities. Kinstrie et al. characterized deletion mutants of the Drosophila class II DYRK, dDYRK2, and demonstrated that a noncatalytic, N-terminal region of the protein was required for autophosphorylation of the activation loop tyrosine, but not for the serine-threonine phosphorylation of substrates. The authors propose that this region, which they term the NAPA domain, acts as a chaperone, analogous to the function of heat shock protein 90 in mediating the autophosphorylation of activation loop tyrosines by the GSK-3 family of kinases, the other family to undergo intramolecular phosphorylation.