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Nuclear Signaling Induced by Ionizing Radiation Involves Colocalization of the Activated p56/p53^lyn Tyrosine Kinase with p34^cdc21

Divisions of Cancer Pharmacology [S. Kh., A. S., Z-M. Y., D. K.] and Cellular and Molecular Biology [S. Kr., L. B. C.], Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, and Department of Radiation and Cellular Oncology, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637 [R. W.]

The Src-like protein-tyrosine kinase p56/p53^lyn 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 p34^cdc2. 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.

¹ This investigation was supported by United States Public Health Service Grant CA55241, awarded by the National Cancer Institute, United States Department of Health and Human Services.

² To whom requests for reprints should be addressed, at Division of Cancer Pharmacology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Received 5/22/96. Accepted 7/10/96.

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