title: Phosphorylation of heterogeneous nuclear ribonucleoprotein K at an extracellular signal-regulated kinase phosphorylation site promotes neurofilament-medium protein expression and axon outgrowth in Xenopus.
abstract: Post-transcriptional control of cytoskeletal genes fine-tunes the supply of structural materials to growing axons in response to extracellular cues. In Xenopus, heterogeneous nuclear ribonucleoprotein K (hnRNPK) plays a crucial role in the nuclear export and translation of multiple cytoskeletal-related mRNAs required for axon outgrowth, and as a substrate of multiple kinases, is thus a likely molecular target of cell signaling pathways regulating such outgrowth. To study the role of hnRNPK's phosphorylation by extracellular signal-regulated kinase (ERK) in Xenopus axon outgrowth, we identified the only ERK1 phosphorylation site on Xenopus hnRNPK (S257; homologous with S284 of human hnRNPK) using an in vitro phosphorylation assay and tested its function in vivo by expressing phosphomimetic (S257D) and phosphodeficient (S257A) forms of hnRNPK in Xenopus embryos. Although neither form altered hnRNPK nuclear export, only the phosphomimetic form significantly rescued both neurofilament protein expression and axon outgrowth from hnRNPK knockdown. This finding represents a previously unidentified function of phosphorylation at this phylogenetically conserved site and implicates hnRNPK as an intracellular molecular target of ERK-mediated signaling in axon outgrowth.
authors.affiliation: Department of Biological Sciences and Center for Neuroscience Research, University at Albany, State University of New York, Albany, NY 12222, USA.
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Hutchins
authors.affiliation: Department of Biological Sciences and Center for Neuroscience Research, University at Albany, State University of New York, Albany, NY 12222, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Belrose
authors.affiliation: Department of Biological Sciences and Center for Neuroscience Research, University at Albany, State University of New York, Albany, NY 12222, USA. Electronic address: bgs86@albany.edu.
authors.forename: Ben G
authors.initials: BG
authors.lastname: Szaro
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D016900:Neurofilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D014981:Xenopus / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C026452:messenger ribonucleoprotein; D048052:Mitogen-Activated Protein Kinase 3
keywords: Axon outgrowth; ERK; Neurofilament; RNA-binding protein; hnRNPK