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Effect of Retinoic Acid on Cellular Content and Human Parathyroid Hormone Activation of Cyclic Adenosine 3':5'-Monophosphate-dependent Protein Kinase Isoenyzmes in Clonal Rat Osteogenic Sarcoma Cells¹

Department of Medicine, University of Melbourne, Repatriation General Hospital, Heidelberg, 3081, Australia [S. A. L., K. W. N., G. R. C., M. K., T. J. M.], and The University of Texas, Health Science Center at Houston, Medical School, Houston, Texas [A. L. S.]

Pretreatment with 10^-8 M retinoic acid for 4 days caused changes in three distinct components of the parathyroid hormone (PTH)-stimulated cyclic adenosine 3':5'-monophosphate response in a clonal rat osteogenic sarcoma cell line, UMR 106-06: (a) the amplitude of the cyclic adenosine 3':5'-monophosphate response to PTH was moderately increased after pretreatment with retinoic acid; (b) while the cellular content of the two isoenzymes of the cyclic adenosine 3':5'-monophosphate-dependent protein kinase was approximately equal in control cells, retinoic acid pretreatment was associated with a marked increase in the ratio of type II to type I holoenzyme activity. This change might be due to a decrease in the type I holoenzyme as suggested by immunofluorescence detection of decreased type I regulatory subunit in fixed cells together with the relative decrease in type I holoenzyme determined biochemically; (c) there was a marked alteration of the pattern of PTH-stimulated protein kinase isoenzyme activation from predominantly type I isoenzyme in control cells to almost exclusively type II isoenzyme in retinoic acid-treated cells. Growth inhibition by submaximal amounts of PTH and retinoic acid when added together was greater than that for either agent alone.

¹ This work was supported by grants from the National Health and Medical Research Council, the Australian Government Department of Veterans' Affairs, and the Children's Leukaemia and Cancer Foundation.

² To whom requests for reprints should be addressed.

Received 1/ 7/85. Revised 5/23/85. Accepted 7/22/85.