NUCLEAR SIGNALING INDUCED BY IONIZING-RADIATION INVOLVES COLOCALIZATION OF THE ACTIVATED P56 P53(LYN) TYROSINE KINASE WITH P34(CDC21)/

The Src-like protein-tyrosine kinase p56/pko(lyn) associates with cell membranes and transduces signals from activated cell surface receptor s, In the present work, cell fractionation and confocal microscopy stu dies demonstrate expression of Lyn in the nucleus, We also demonstrate that exposure of intact cells to ionizing radiation is associated wit h selective activation of nuclear Lyn, Similar findings have been obta ined following irradiation of purified nuclei, Immunoprecipitation stu dies of nuclear lysates demonstrate radiation-induced binding of Lyn t o p34(cdc2), Nuclear colocalization of Lyn with Cdc2 has been confirme d by confocal microscopy, Other studies with glutathione S-transferase -Lyn fusion proteins demonstrate that the binding of Lyn to nuclear Cd c2 is associated with inhibition of Cdc2 activity. These findings sugg est that the association of activated Lyn with Cdc2 in the nucleus may contribute to regulation of a DNA damage-dependent premitotic checkpo int.