Chemical inhibition of a subset of Arabidopsis thaliana GSK3-like kinases activates brassinosteroid signaling.
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.
De Rybel
Bert
B
Department of Plant Systems Biology, VIB, Technologiepark 927, B-9052 Gent, Belgium.
Audenaert
Dominique
D
Vert
Grégory
G
Rozhon
Wilfried
W
Mayerhofer
Juliane
J
Peelman
Frank
F
Coutuer
Silvie
S
Denayer
Tinneke
T
Jansen
Leentje
L
Nguyen
Long
L
Vanhoutte
Isabelle
I
Beemster
Gerrit T S
GT
Vleminckx
Kris
K
Jonak
Claudia
C
Chory
Joanne
J
Inzé
Dirk
D
Russinova
Eugenia
E
Beeckman
Tom
T
D000595:Amino Acid Sequence; D000631:Aminopyridines / Q000737:chemistry / Q000494:pharmacology*; D017360:Arabidopsis / Q000201:enzymology*; D029681:Arabidopsis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D060406:Brassinosteroids; D002777:Cholestanols / Q000737:chemistry / Q000494:pharmacology*; D004268:DNA-Binding Proteins; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013260:Steroids, Heterocyclic / Q000737:chemistry / Q000494:pharmacology*; D013386:Succinates / Q000737:chemistry / Q000494:pharmacology*
D000631:Aminopyridines; D029681:Arabidopsis Proteins; D060406:Brassinosteroids; D002777:Cholestanols; D004268:DNA-Binding Proteins; D038362:Glycogen Synthase Kinase 3; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011494:Protein Kinases; D013260:Steroids, Heterocyclic; D013386:Succinates; C456160:BES1 protein, Arabidopsis; C543414:bikinin; C448985:At4g18710 protein, Arabidopsis; C108270:BRI1 protein, Arabidopsis; C023623:brassinolide