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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Regulation of Dyrk1A kinase activity by 14-3-3.

Dual-specificity tyrosine(Y) regulated kinase 1A (DYRK1A) is a serine/threonine protein kinase implicated in mental retardation resulting from Down syndrome. In this study, we carried out yeast two-hybrid screening to find proteins regulating DYRK1A kinase activity. We identified 14-3-3 as a Dyrk1A interacting protein, which is consistent with the previous finding of the interaction between the yeast orthologues Yak1p and Bmh1/2p. We showed the interaction between Dyrk1A and 14-3-3 in vitro and in vivo. The binding required the N-terminus of Dyrk1A and was independent of the Dyrk1A phosphorylation status. Functionally, 14-3-3 binding increased Dyrk1A kinase activity in a dose dependent manner in vitro. In vivo, a small peptide inhibiting 14-3-3 binding, sc138, decreased Dyrk1A kinase activity in COS7. In summary, these results suggest that DYRK1A kinase activity could be regulated by the interaction of 14-3-3.[1]


  1. Regulation of Dyrk1A kinase activity by 14-3-3. Kim, D., Won, J., Shin, D.W., Kang, J., Kim, Y.J., Choi, S.Y., Hwang, M.K., Jeong, B.W., Kim, G.S., Joe, C.O., Chung, S.H., Song, W.J. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
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