Specific and direct binding of protein kinase C to an immobilized tamoxifen analogue
O'Brian, C.A.; Housey, G.M.; Weinstein, I.B.
Cancer Research 48(13): 3626-3629
1988
ISSN/ISBN: 0008-5472 PMID: 3378206 Document Number: 314018
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.