title: PKC-mediated phosphorylation of nuclear lamins at a single serine residue regulates interphase nuclear size inXenopusand mammalian cells.
abstract: How nuclear size is regulated is a fundamental cell-biological question with relevance to cancers, which often exhibit enlarged nuclei. We previously reported that conventional protein kinase C (cPKC) contributes to nuclear size reductions that occur during earlyXenopusdevelopment. Here we report that PKC-mediated phosphorylation of lamin B3 (LB3) contributes to this mechanism of nuclear size regulation. By mapping PKC phosphorylation sites on LB3 and testing the effects of phosphomutants inXenopus laevisembryos, we identify the novel site S267 as being an important determinant of nuclear size. Furthermore, FRAP studies demonstrate that phosphorylation at this site increases lamina dynamics, providing a mechanistic explanation for how PKC activity influences nuclear size. We subsequently map thisX. laevisLB3 phosphorylation site to a conserved site in mammalian lamin A (LA), S268. Manipulating PKC activity in cultured mammalian cells alters nuclear size, as does expression of LA-S268 phosphomutants. Taken together, these data demonstrate that PKC-mediated lamin phosphorylation is a conserved mechanism of nuclear size regulation.
authors.affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Edens
authors.affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dilsaver
authors.affiliation: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071 dlevy1@uwyo.edu.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Levy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000502:physiology; D053145:Cell Nucleus Size / Q000502:physiology*; D007382:Intermediate Filaments / Q000378:metabolism; D007399:Interphase / Q000502:physiology; D034904:Lamin Type A / Q000378:metabolism; D034921:Lamin Type B / Q000378:metabolism; D034882:Lamins / Q000378:metabolism; D008322:Mammals / Q000378:metabolism; D034881:Nuclear Lamina / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology; D012694:Serine / Q000378:metabolism; D014981:Xenopus / Q000378:metabolism
chemical_list: D034904:Lamin Type A; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D012694:Serine; D011493:Protein Kinase C