The role of bcl-2 in the signal transduction pathway was assessed by studying the inositol phospholipid metabolism in fibroblasts transfected by this oncogene. The rate of accumulation of water soluble inositol phosphates in response to several growth factors was much higher in bcl-2 transfected NIH3T3 clones than in untransfected control. Moreover, bcl-2 transfected clones express elevated levels of phosphatidic acid, a phospholipid produced during receptor stimulated breakdown of phosphoinositides. Our findings suggest that the expression of bcl-2 in NIH3T3 fibroblasts leads to the coupling of growth factor receptors to stimulate inositol phosphate production, henceforth establishing its role in the growth factor receptor mediated signal transduction pathway.

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This work was supported by National Cancer Institute Grant CA 39860 and American Cancer Society Grant CH 378 awarded to C. M. C.

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