title: Regulation of protein kinase CK1alphaLS by dephosphorylation in response to hydrogen peroxide.
abstract: Low levels of hydrogen peroxide (H(2)O(2)) are mitogenic to mammalian cells and stimulate the hyperphosphorylation of heterogeneous nuclear ribonucleoprotein C (hnRNP-C) by protein kinase CK1alpha. However, the mechanisms by which CK1alpha is regulated have been unclear. Here it is demonstrated that low levels of H(2)O(2) stimulate the rapid dephosphorylation of CK1alphaLS, a nuclear splice form of CK1alpha. Furthermore, it is demonstrated that either treatment of endothelial cells with H(2)O(2), or dephosphorylation of CK1alphaLS in vitro enhances the association of CK1alphaLS with hnRNP-C. In addition, dephosphorylation of CK1alphaLS in vitro enhances the kinase's ability to phosphorylate hnRNP-C. While CK1alpha appears to be present in all metazoans, analysis of CK1alpha genomic sequences from several species reveals that the alternatively spliced nuclear localizing L-insert is unique to vertebrates, as is the case for hnRNP-C. These observations indicate that CK1alphaLS and hnRNP-C represent conserved components of a vertebrate-specific H(2)O(2)-responsive nuclear signaling pathway.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Simches Research Building, Boston, MA 02114, USA.
authors.forename: Shahinaz
authors.initials: S
authors.lastname: Bedri
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Cizek
authors.forename: Iryna
authors.initials: I
authors.lastname: Rastarhuyeva
authors.forename: James R
authors.initials: JR
authors.lastname: Stone
mesh_terms: D000595:Amino Acid Sequence; D047389:Casein Kinase I / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D019154:Protein Splicing; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D047389:Casein Kinase I