Regulation of protein kinase CK1alphaLS by dephosphorylation in response to hydrogen peroxide.
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.
Bedri
Shahinaz
S
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Simches Research Building, Boston, MA 02114, USA.
Cizek
Stephanie M
SM
Rastarhuyeva
Iryna
I
Stone
James R
JR
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
D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D047389:Casein Kinase I