AMP-activated Protein Kinase Up-regulates Mitogen-activated Protein (MAP) Kinase-interacting Serine/Threonine Kinase 1a-dependent Phosphorylation of Eukaryotic Translation Initiation Factor 4E

• Published in: The Journal of biological chemistry 2016-08, Vol.291 (33), p.17020-17027
• Main Authors: Zhu, Xiaoqing, Dahlmans, Vivian, Thali, Ramon, Preisinger, Christian, Viollet, Benoit, Voncken, J. Willem, Neumann, Dietbert
• Format: Article
• Language: English
• Subjects: Accelerated Communications; AMP-activated kinase (AMPK); AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; Cell Line, Tumor; Eukaryotic Initiation Factor-4E - chemistry; Eukaryotic Initiation Factor-4E - genetics; Eukaryotic Initiation Factor-4E - metabolism; eukaryotic translation initiation factor 4E (eIF4E); Humans; Intracellular Signaling Peptides and Proteins - chemistry; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; MAP kinase-interacting serine/threonine protein kinase 1a (MNK1a); mitogen-activated protein kinase (MAPK); Models, Molecular; Phosphorylation; post-translational modification (PTM); protein phosphorylation; Protein Structure, Secondary; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; translation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.C116.740498

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 Ser353 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-Ser353 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-Ser353 phosphorylation in regulation of the MNK1a kinase, which correlates with increased eIF4E phosphorylation in vitro and in vivo.