title: Nuclear signaling induced by ionizing radiation involves colocalization of the activated p56/p53lyn tyrosine kinase with p34cdc2.
abstract: The Src-like protein-tyrosine kinase p56/p53lyn associates with cell membranes and transduces signals from activated cell surface receptors. In the present work, cell fractionation and confocal microscopy studies demonstrate expression of Lyn in the nucleus. We also demonstrate that exposure of intact cells to ionizing radiation is associated with selective activation of nuclear Lyn. Similar findings have been obtained following irradiation of purified nuclei. Immunoprecipitation studies of nuclear lysates demonstrate radiation-induced binding of Lyn to p34cdc2. Nuclear colocalization of Lyn with Cdc2 has been confirmed by confocal microscopy. Other studies with glutathione S-transferase-Lyn fusion proteins demonstrate that the binding of Lyn to nuclear Cdc2 is associated with inhibition of Cdc2 activity. These findings suggest that the association of activated Lyn with Cdc2 in the nucleus may contribute to regulation of a DNA damage-dependent premitotic checkpoint.
authors.affiliation: Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kharbanda
authors.forename: A
authors.initials: A
authors.lastname: Saleem
authors.forename: Z M
authors.initials: ZM
authors.lastname: Yuan
authors.forename: S
authors.initials: S
authors.lastname: Kraeft
authors.forename: R
authors.initials: R
authors.lastname: Weichselbaum
authors.forename: L B
authors.initials: LB
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Kufe
mesh_terms: D016203:CDC2 Protein Kinase / Q000032:analysis* / Q000378:metabolism; D002467:Cell Nucleus / Q000201:enzymology / Q000528:radiation effects*; D004249:DNA Damage; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D010766:Phosphorylation; D019061:src-Family Kinases / Q000032:analysis* / Q000378:metabolism
chemical_list: C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D016203:CDC2 Protein Kinase