14-3-3 Interacts with LKB1 via recognizing phosphorylated threonine 336 residue and suppresses LKB1 kinase function

Here we report a regulatory mechanism by which LKB1 is controlled by 14-3-3 proteins through phorsphorylation of Thr336. The results from the current study indicate that 14-3-3 zeta inhibits LKB1 from phosphorylating its substrate, AMPK (AMP-dependent protein kinase) and attenuates LKB1-mediated G1 cell cycle arrest and apoptosis by interfering with the interaction between LKB1 and its substrates. This regulation does not change either the LKB1 catalytic activity or subcellular localization of LKB1. Moreover, we demonstrate that serum starvation enhances LKB1 activity and increases the phosphorylation of Thr336. Taken together, our results suggest that autophosphorylation of Thr336 acts as an activating signal for LKB1 to recruit 14-3-3, which in turn attenuates the activation of LKB1 to keep the activity of LKB1 in check. Structured summary of protein interactions: LKB1 binds to 14-3-3 eta by pull down (View interaction) LKB1 physically interacts with 14-3-3 zeta and AMPKalpha1 by pull down (View interaction) LKB1 physically interacts with 14-3-3 zeta by pull down (View Interaction: 1, 2, 3) LKB1 binds to 14-3-3 zeta by pull down (View interaction) LKB1 binds to 14-3-3 tau by pull down (View interaction) LKB1 binds to 14-3-3 gamma by pull down (View interaction) LKB1 and 14-3-3 zeta colocalize by fluorescence microscopy (View interaction). (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.