title: 14-3-3 interacts with LKB1 via recognizing phosphorylated threonine 336 residue and suppresses LKB1 kinase function.
abstract: 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 ζ 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.
authors.affiliation: School of Life Sciences, Anhui University, Hefei, Anhui 230039, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.forename: Tao
authors.initials: T
authors.lastname: Zhou
authors.forename: Haian
authors.initials: H
authors.lastname: Fu
authors.forename: Hanyan
authors.initials: H
authors.lastname: Sun
authors.forename: Bei
authors.initials: B
authors.lastname: Huang
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D013912:Threonine; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases