title: Regulation of Dyrk1A kinase activity by 14-3-3.
abstract: 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.
authors.affiliation: Division of CNS, Hanwha Chemical R&D Center, Daejon 305-345, Republic of Korea.
authors.forename: Doyeun
authors.initials: D
authors.lastname: Kim
authors.forename: Jungyeon
authors.initials: J
authors.lastname: Won
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Shin
authors.forename: Junghee
authors.initials: J
authors.lastname: Kang
authors.forename: Yeon Ju
authors.initials: YJ
authors.lastname: Kim
authors.forename: Su Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Hwang
authors.forename: Byeong-Woo
authors.initials: BW
authors.lastname: Jeong
authors.forename: Gun Soo
authors.initials: GS
authors.lastname: Kim
authors.forename: Cheol O
authors.initials: CO
authors.lastname: Joe
authors.forename: Sul-Hee
authors.initials: SH
authors.lastname: Chung
authors.forename: Woo-Joo
authors.initials: WJ
authors.lastname: Song
mesh_terms: D048948:14-3-3 Proteins; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003067:Coenzymes / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry* / Q000378:metabolism*; D000097603:Dyrk Kinases
chemical_list: D048948:14-3-3 Proteins; D003067:Coenzymes; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D014446:Tyrosine 3-Monooxygenase; D000097603:Dyrk Kinases