Research ArticleKinases

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

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

You are currently viewing the abstract.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.


Dual-specificity tyrosine phosphorylation–regulated kinases (DYRKs) autophosphorylate an essential tyrosine residue in their activation loop and phosphorylate their substrates on serine and threonine residues. Phosphorylation of the activation loop tyrosine occurs intramolecularly, is mediated by a short-lived transitional intermediate during protein maturation, and is required for functional serine-threonine kinase activity of DYRKs. The DYRK family is separated into two subclasses. Through bioinformatics and mutational analyses, we identified a conserved domain in the noncatalytic N terminus of a class 2 DYRK that was required for autophosphorylation of the activation loop tyrosine but not for the phosphorylation of serine or threonine residues in substrates. We propose that this domain, which we term the NAPA domain, provides a chaperone-like function that transiently converts class 2 DYRKs into intramolecular kinases capable of autophosphorylating the activation loop tyrosine. The conservation of the NAPA domain from trypanosomes to humans indicates that this form of intramolecular phosphorylation of the activation loop is ancient and may represent a primordial mechanism for the activation of protein kinases.

View Full Text