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Retinoic Acid-induced Rapid Loss of Nuclear Cyclic AMP-dependent Protein Kinase in Teratocarcinoma Cells¹

Unité INSERM 188, 74 avenue Denfert Rochereau, 75014 Paris, France [A. P., D. E-B., P. G.], and Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland 20892 [W. B. A.]

To determine what effect retinoic acid might have in modulating cyclic AMP-mediated events at the nucleus of teratocarcinoma cells, we have investigated the effect of retinoic acid treatment of F9 and PC13 cells on cyclic AMP-dependent protein kinase activity and the amounts of the RI and RII cyclic AMP binding proteins present in the nuclear fraction. Exposure of F9 cells to retinoic acid (0.1 µM) induces differentiation to parietal endoderm, while retinoic acid treatment (3 µM) of PC13 cells induces differentiation to visceral endoderm. In both cell types retinoic acid treatment causes a rapid (within 4 h) and pronounced (by 2-fold) decrease in nuclear cyclic AMP-dependent protein kinase activity. Conversely, as measured by cyclic [8-azido-³²P]AMP photoaffinity labeling a similar rapid and pronounced decrease in the RI and RII regulatory subunits is observed at the nucleus. This decrease in nuclear cyclic AMP-dependent protein kinases in at least two cell types may be an early event of retinoid action important in the initiation of differentiation.

¹ This investigation was supported by a grant from Le Comité de Paris de la Ligue Nationale Française contre le Cancer.

² To whom requests for reprints should be addressed.

Received 3/16/87. Revised 6/ 9/87. Accepted 7/30/87.