AMP-activated Protein Kinase Up-regulates Mitogen-activated Protein (MAP) Kinase-interacting Serine/Threonine Kinase 1a-dependent Phosphorylation of Eukaryotic Translation Initiation Factor 4E.
AMP-activated protein kinase (AMPK) is a molecular energy sensor that acts to sustain cellular energy balance. Although AMPK is implicated in the regulation of a multitude of ATP-dependent cellular processes, exactly how these processes are controlled by AMPK as well as the identity of AMPK targets and pathways continues to evolve. Here we identify MAP kinase-interacting serine/threonine protein kinase 1a (MNK1a) as a novel AMPK target. Specifically, we show AMPK-dependent Ser(353) phosphorylation of the human MNK1a isoform in cell-free and cellular systems. We show that AMPK and MNK1a physically interact and that in vivo MNK1a-Ser(353) phosphorylation requires T-loop phosphorylation, in good agreement with a recently proposed structural regulatory model of MNK1a. Our data suggest a physiological role for MNK1a-Ser(353) phosphorylation in regulation of the MNK1a kinase, which correlates with increased eIF4E phosphorylation in vitro and in vivo.
['Zhu|Xiaoqing|X|', 'Dahlmans|Vivian|V|', 'Thali|Ramon|R|', 'Preisinger|Christian|C|', 'Viollet|Benoit|B|', 'Voncken|J Willem|JW|', 'Neumann|Dietbert|D|0000-0002-4316-684X']
D055372:AMP-Activated Protein Kinases D000818:Animals D045744:Cell Line, Tumor D039561:Eukaryotic Initiation Factor-4E D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D008958:Models, Molecular D010766:Phosphorylation D017346:Protein Serine-Threonine Kinases D017433:Protein Structure, Secondary
translation MAP kinase-interacting serine/threonine protein kinase 1a (MNK1a) AMP-activated kinase (AMPK) eukaryotic translation initiation factor 4E (eIF4E) mitogen-activated protein kinase (MAPK) post-translational modification (PTM) protein phosphorylation