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.
Kim
Doyeun
D
Division of CNS, Hanwha Chemical R&D Center, Daejon 305-345, Republic of Korea.
Won
Jungyeon
J
Shin
Dong Wook
DW
Kang
Junghee
J
Kim
Yeon Ju
YJ
Choi
Su Young
SY
Hwang
Mi-Kyung
MK
Jeong
Byeong-Woo
BW
Kim
Gun Soo
GS
Joe
Cheol O
CO
Chung
Sul-Hee
SH
Song
Woo-Joo
WJ
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
D048948:14-3-3 Proteins; D003067:Coenzymes; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D014446:Tyrosine 3-Monooxygenase; D000097603:Dyrk Kinases