The postreceptor signaling pathway(s) that mediates the effects of transforming growth factor-β1 (TGF-β1) is incompletely understood. The present study investigated the involvement of protein kinase C (PKC) in the growth-inhibitory action of TGF-β1 in PC3, a human prostate cancer cell line. PKCα, the only conventional PKC isoform detected in PC3 cells, appeared to be constitutively active based on its presence in both Triton- soluble membrane fraction and cytosol. However, levels of membrane-associated PKCα were decreased by a growth-inhibitory dose of TGF-β1. The response to TGF-β1 was rapid (within 5 min), time dependent, isoform specific, and occurred without apparent changes in levels of total PKCα protein. TGF-β1 also decreased the levels of membrane-associated PKC activity coincident with its inhibitory effect on PKCα's membrane association. Inhibition of PKC activity appeared to be associated with growth inhibition in PC3 cells, because chelerythrine (a specific PKC inhibitor) likewise decreased cell proliferation. Taken together, our data suggest that inhibition of PKC activity, at least in part due to inactivation of PKCα, is an early event associated with TGF-β1 postreceptor signaling that might mediate suppression of cell proliferation.
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