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Ionizing Radiation Induces Rapid Tyrosine Phosphorylation of p34^cdc21

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

Eukaryotic cells respond to ionizing radiation exposure with cell cycle arrest. However, little is known about the signaling mechanisms responsible for this effect. The present work has asked whether ionizing radiation exposure is associated with changes in phosphorylation of proteins in HL-60 myeloid leukemia cells. The results demonstrate increased tyrosine phosphorylation of a M_r 34,000 substrate. This effect was detectable at 1 to 10 min after irradiation and was induced by doses of 50 to 500 cGy. Immunoprecipitation studies further suggest that this substrate is the serine/threonine p34^cdc2 protein kinase. Since p34^cdc2 is required for entry into mitosis, these findings support the posttranslational modification of a cell cycle regulatory protein in the response to ionizing radiation.

¹ This investigation was supported by PHS Grant CA55241 awarded by the National Cancer Institute, DHHS.

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

Received 12/ 6/93. Accepted 2/ 4/94.

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