Editors' ChoiceKinases

New Substrates for DYRK

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Science's STKE  01 May 2001:
Vol. 2001, Issue 80, pp. tw9
DOI: 10.1126/stke.2001.80.tw9

Two papers have identified new substrates for dual-specificity tyrosine-phosphorylated and regulated kinases 1A and 2 (DYRK1A and DYRK2). In the first paper by Woods et al., DYRK1A is identified as a contaminating kinase in an in vitro assay for the phosphorylation of the mammalian forkhead transcription factor FKHR by protein kinase B (PKB). FKHR was phosphorylated on a novel site in vitro by DYRK1A, separate from the known PKB phosphorylation sites, and this DYRK1A site was constitutively phosphorylated in vivo. Mutation of the DYRK1A phosphorylation site enhanced transcriptional activation of a reporter gene by FKHR but did not interfere with the repression of FKHR activity in response to insulin. The second Woods et al. paper demonstrates that the cytosolic isoform of DYRK, DYRK2, was able to phosphorylate the translation initiation factor eIF2Bε, which was required for glycogen synthase kinase 3 (GSK3) to phosphorylate eIF2Bε on another site in an in vitro assay. DYRK1A or DYRK2 were also able to phosphorylate the microtubule-associated protein tau, allowing tau to be a substrate for GSK3 in vitro. GSK3 and FKHR are both regulated by growth factor signaling. These two papers suggest new roles for the DYRKs in controlling cellular responsiveness to growth factor signaling pathways.

Y. L. Woods, G. Rena, N. Morrice, A. Barthel, W. Becker, S. Guo, T. G. Unterman, P. Cohen, The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site. Biochem. J. 355, 597-607 (2001). [Online Journal]

Y. L. Woods, P. Cohen, W. Becker, R. Jakes, M. Goedert, X. Wang, C. G. Proud, The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bε at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3 -priming kinase. Biochem. J. 355, 609-615 (2001). [Online Journal]