title: AMP-activated Protein Kinase Up-regulates Mitogen-activated Protein (MAP) Kinase-interacting Serine/Threonine Kinase 1a-dependent Phosphorylation of Eukaryotic Translation Initiation Factor 4E.
abstract: 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.
authors.affiliation: From the Department of Molecular Genetics, CARIM School of Cardiovascular Diseases and.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Molecular Genetics, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.
authors.forename: Vivian
authors.initials: V
authors.lastname: Dahlmans
authors.affiliation: the Institute of Cell Biology, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Ramon
authors.initials: R
authors.lastname: Thali
authors.affiliation: the Proteomics Facility, Interdisciplinary Center for Clinical Research (IZKF), RWTH University Hospital Aachen, 52074 Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Preisinger
authors.affiliation: the INSERM U1016, Institut Cochin, Department of Endocrinology, Metabolism and Diabetes, 75014 Paris, France, the CNRS UMR 8104, 75014 Paris, France, and the Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.affiliation: Department of Molecular Genetics, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands.
authors.forename: J Willem
authors.initials: JW
authors.lastname: Voncken
authors.affiliation: From the Department of Molecular Genetics, CARIM School of Cardiovascular Diseases and the Institute of Cell Biology, ETH Zurich, 8093 Zurich, Switzerland, d.neumann@maastrichtuniversity.nl.
authors.forename: Dietbert
authors.identifier: 0000-0002-4316-684X
authors.initials: D
authors.lastname: Neumann
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D039561:Eukaryotic Initiation Factor-4E / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D047908:Intracellular Signaling Peptides and Proteins; C000601282:eIF4E protein, mouse; C491395:MKNK1 protein, human; C106281:Mknk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated kinase (AMPK); MAP kinase-interacting serine/threonine protein kinase 1a (MNK1a); eukaryotic translation initiation factor 4E (eIF4E); mitogen-activated protein kinase (MAPK); post-translational modification (PTM); protein phosphorylation; translation