title: Two conserved serines in the nuclear localization signal flanking region are involved in the nuclear targeting of human lamin A.
abstract: The nuclear lamins are karyophilic proteins located at the nucleoplasmic surface of the inner nuclear membrane. We have constructed mutants immediately N-terminal to the nuclear localization signal of human lamin A to identify sites regulating the nuclear transport of the protein. Using an in vitro transport assay, we determined the short-term kinetics of nucleocytoplasmic transport of wild type and mutant proteins. The double mutation of two putative protein kinase C sites (serine 403/404-->alanine) reduced the rate of nuclear import for the mutant protein. Inhibition of phosphorylation in wild type lamin A by the specific protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) and staurosporine or treatment with acid or alkaline phosphatase decreased the nuclear import of the protein. We suggest that transport of human lamin A into the nucleus is regulated by phosphorylations of protein kinase C sites in the sequence N-terminal to the nuclear localization signal.
authors.affiliation: Genetisches Institut, Justus-Liebig-Universität, Giessen/Germany.
authors.forename: M
authors.initials: M
authors.lastname: Leukel
authors.forename: E
authors.initials: E
authors.lastname: Jost
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000135:Acid Phosphatase / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D002642:Chick Embryo; D016384:Consensus Sequence; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D034904:Lamin Type A; D034882:Lamins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021382:Protein Sorting Signals / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D019311:Staurosporine
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D034904:Lamin Type A; D034882:Lamins; D009687:Nuclear Proteins; D010879:Piperazines; D021382:Protein Sorting Signals; D012694:Serine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D019311:Staurosporine