BX517, an inhibitor of the mammalian phospholipid-dependent kinase 1 (PDK1), antagonizes sucrose-induced plant growth and represses the target of rapamycin (TOR) signaling and the cell cycle through WEE1 kinase in Arabidopsis thaliana.

The target of rapamycin (TOR) signaling pathway is critical for plant growth and stress adaptation through maintaining the proper balance between cell proliferation and differentiation. Here, by using BX517, an inhibitor of the mammalian phosphoinositide-dependent protein kinase 1 (PDK1), we tested the hypothesis that a plant ortholog of PDK1 could influence the TOR complex activity and its target, the S6 ribosomal protein kinase (S6K) in Arabidopsis seedlings. Through locally applying sucrose to leaves, which promotes root growth and plant biomass production via TOR signaling, we could demonstrate the opposite trend upon BX517 treatment, which antagonized sucrose-induced plant growth and overly decreased root development through inhibiting the expression of mitotic cyclins CYCB1 and CYCA3 in root meristems. Evidence was gathered that the WEE1 kinase, a master regulator of the DNA damage rescue system in meristems, operates downstream of a plant BX517 target(s). TOR protein activity and WEE1 expression were analyzed through protein blots and reporter gene activity, respectively, and their relationship with meristematic cell cycle progression was tested through genetic analyses. BX517 reduced TOR kinase activity, activated WEE1 expression in shoot, root, and lateral root meristems, and inhibited meristematic cell cycle progression in roots, suggesting that PDK1 is a critical element for plant responses to mitogenic factors through modulating TOR activity. Our data uncover a relation between a PDK1 ortholog with TOR activity and the expression of WEE1 kinase for growth and stress responses in plants.