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Specific and Direct Binding of Protein Kinase C to an Immobilized Tamoxifen Analogue

Comprehensive Cancer Center and Institute of Cancer Research [C. A. O., G. M. H., I. B. W.], Department of Medicine [I. B. W.], and Department of Genetics and Development [G. M. H.], College of Physicians and Surgeons, Columbia University, New York, New York 10032

We have previously demonstrated that tamoxifen and related triphenylethylene compounds are potent inhibitors of protein kinase C (PKC). The present study demonstrates that PKC binds specifically and reversibly to the antiestrogen N-didesmethyltamoxifen when the drug is coupled to CNBr-activated agarose through its primary amine, in the absence of lipid and other cofactors of the enzyme. PKC did not bind to 4-hydroxytamoxifen, which had been immobilized on epoxy-activated Sepharose through its hydroxyl moiety. This shows that the binding of PKC to immobilized N-didesmethyltamoxifen was not merely due to hydrophobic interactions, since N-didesmethyltamoxifen and 4-hydroxytamoxifen have nearly identical hydrophobicities. These results demonstrate that PKC has specific triphenylethylene-binding sites, which may mediate the inhibition of PKC activity by these antiestrogens.

¹ Present address: Department of Cell Biology, The University of Texas System Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. To whom requests for reprints should be addressed.

Received 12/ 3/87. Revised 3/ 3/88. Accepted 4/ 5/88.

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