ALPHA-THROMBIN-INDUCED NUCLEAR SN-1,2-DIACYLGLYCEROLS ARE DERIVED FROM PHOSPHATIDYLCHOLINE HYDROLYSIS IN CULTURED FIBROBLASTS

Diglycerides play an important role in a number of agonist-induced sig nal transduction pathways. We have recently demonstrated that a-thromb in induces a rapid increase in the level of diglyceride mass in the nu cleus and a selective increase in nuclear PKC-alpha [Leach, K. L., Ruf f, V. A., Jarpe, M. B., Fabbro, D., Adams, L. D., & Raben, D. M. (I 99 2) J. Biol. Chem. 267, 21816-218221. In the present report, we examine d the potential source of the induced nuclear diglycerides by examinin g the molecular species profiles of both the induced diglycerides and nuclear phospholipids by capillary gas chromatography. The molecular s pecies profiles of the nuclear diglycerides generated resemble the spe cies profiles of PC, and not PI species, at all times. In addition, wh ile our previous data indicated that the molecular species of whole-ce ll phospholipids did not change in response to alpha-thrombin, nuclear PE was altered in a dramatic and selective manner in response to this agonist. These results demonstrate that PC hydrolysis is the predomin ant, if not exclusive, source of the alpha-thrombin-induced nuclear di glycerides in these fibroblasts.