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Subcellular Distribution of Protein Kinase C in Rat Colonic Epithelial Cells with Different Proliferative Activities¹

Department of Medicine, Veterans Administration Medical Center and University of Pittsburgh, Pittsburgh, Pennsylvania 15240

Activation of Ca²⁺ and phospholipid-dependent protein kinase C (PKC) is associated with increased proliferation in several cell types. When activated, PKC is tightly bound to the particulate cell fraction. Accordingly, we examined the subcellular distribution of PKC in superficial (nonproliferative) and proliferative colonic epithelial cells from rat colonic mucosa. PKC was determined in soluble and particulate fractions of these cells following partial purification of enzyme activity of cellular homogenates by DEAE-cellulose chromatography. In the superficial cells, 90% of the PKC was associated with the soluble fraction. By contrast only 42% of the enzyme activity was found in the soluble fraction of proliferative cells. The specific activity of protein kinase C was higher in the particulate fraction of proliferative compared to superficial cells when expressed as a function of either particulate protein or cellular DNA content. Addition of deoxycholate or 12-O-tetradecanoylphorbol-13-acetate induced a translocation of protein kinase C from the soluble to the particulate fraction. [³H]Thymidine incorporation into DNA was higher in colonic epithelial cells isolated from the colons of rats which had been exposed to deoxycholate or 12-O-tetradecanoylphorbol-13-acetate in vivo. Treatment of rats with 1-(5-isoquinolinyl)-2-methylpiperazine (H-7) suppressed basal [³H]thymidine incorporation into DNA and increases in this parameter induced by 12-O-tetradecanoylphorbol-13-acetate and deoxycholate. The results are consistent with a positive role for activation of protein kinase C in the control of colonic epithelial proliferation.

¹ This work was supported by Grant CA31680 from the National Cancer Institute through the Large Bowel Cancer Project.

² To whom requests for reprints should be addressed, at the Veterans Administration Medical Center, University Drive C, Pittsburgh, PA 15240.

Received 11/25/86. Revised 3/25/87. Accepted 4/ 9/87.

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