TY - JOUR
T1 - Chemical Inhibition of a Subset of Arabidopsis thaliana GSK3-like Kinases Activates Brassinosteroid Signaling
AU - De Rybel, Bert
AU - Audenaert, Dominique
AU - Vert, Grégory
AU - Rozhon, Wilfried
AU - Mayerhofer, Juliane
AU - Peelman, Frank
AU - Coutuer, Silvie
AU - Denayer, Tinneke
AU - Jansen, Leentje
AU - Nguyen, Long
AU - Vanhoutte, Isabelle
AU - Beemster, Gerrit T.S.
AU - Vleminckx, Kris
AU - Jonak, Claudia
AU - Chory, Joanne
AU - Inzé, Dirk
AU - Russinova, Eugenia
AU - Beeckman, Tom
N1 - Funding Information:
We thank Jenny Bain, Hilary McLaughlan, and Philip Cohen for analyzing the effect of bikinin on a panel of 77 human kinases, Eveline Van De Slijke for help with western blots, Natalie De Jonge for helpful discussions on the SPR experiments, Karel Spruyt for graphics support, and Martine De Cock for help in preparing the manuscript. This work was supported in part by a grant from the U.S. National Science Foundation (to J.C.), by the Austrian Science foundation (grant to C. J.), the Interuniversity Attraction Poles Programme (IUAP VI/33), initiated by the Belgian State, Science Policy Office, and the Special Research Fund of Ghent University (predoctoral fellowship to B.D.R.). D.A. is a Postdoctoral Fellow of the Research Foundation-Flanders (FWO). D.A. and L.N. are part of the VIB Compound Screening Facility.
PY - 2009/6/26
Y1 - 2009/6/26
N2 - Glycogen synthase kinase 3 (GSK3) is a key regulator in signaling pathways in both animals and plants. Three Arabidopsis thaliana GSK3s are shown to be related to brassinosteroid (BR) signaling. In a phenotype-based compound screen we identified bikinin, a small molecule that activates BR signaling downstream of the BR receptor. Bikinin directly binds the GSK3 BIN2 and acts as an ATP competitor. Furthermore, bikinin inhibits the activity of six other Arabidopsis GSK3s. Genome-wide transcript analyses demonstrate that simultaneous inhibition of seven GSK3s is sufficient to activate BR responses. Our data suggest that GSK3 inhibition is the sole activation mode of BR signaling and argues against GSK3-independent BR responses in Arabidopsis. The opportunity to generate multiple and conditional knockouts in key regulators in the BR signaling pathway by bikinin represents a useful tool to further unravel regulatory mechanisms.
AB - Glycogen synthase kinase 3 (GSK3) is a key regulator in signaling pathways in both animals and plants. Three Arabidopsis thaliana GSK3s are shown to be related to brassinosteroid (BR) signaling. In a phenotype-based compound screen we identified bikinin, a small molecule that activates BR signaling downstream of the BR receptor. Bikinin directly binds the GSK3 BIN2 and acts as an ATP competitor. Furthermore, bikinin inhibits the activity of six other Arabidopsis GSK3s. Genome-wide transcript analyses demonstrate that simultaneous inhibition of seven GSK3s is sufficient to activate BR responses. Our data suggest that GSK3 inhibition is the sole activation mode of BR signaling and argues against GSK3-independent BR responses in Arabidopsis. The opportunity to generate multiple and conditional knockouts in key regulators in the BR signaling pathway by bikinin represents a useful tool to further unravel regulatory mechanisms.
KW - CHEMBIO
UR - https://www.scopus.com/pages/publications/67649795054
U2 - 10.1016/j.chembiol.2009.04.008
DO - 10.1016/j.chembiol.2009.04.008
M3 - Article
C2 - 19549598
AN - SCOPUS:67649795054
SN - 1074-5521
VL - 16
SP - 594
EP - 604
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 6
ER -