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J. Biol. Chem. 277 (46): 44327-44331

© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

Zinc Release from Protein Kinase C as the Common Event during Activation by Lipid Second Messenger or Reactive Oxygen*

Irina KorichnevaDagger , Beatrice Hoyos, Ramon Chua, Ester Levi, and Ulrich Hammerling

From the Program in Immunology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021

Zinc is a structural component of many regulatory molecules including transcription factors and signaling molecules. We report that two alternate signaling pathways of protein kinase C (PKC) activation involving either the lipid second messengers (diacylglycerol and its mimetics, the phorbol esters) or reactive oxygen converge at the zinc finger of the regulatory domain. They all trigger the release of zinc ions. An increase in intracellular free Zn2+ was observed by confocal microscopy in intact cells treated with phorbol ester or by mild oxidation. The source of liberated Zn2+ was traced to PKC and particularly the zinc finger domains. The activated form of native PKCalpha contained significantly less Zn2+ than the resting form. Furthermore, purified recombinant PKC protein fragments shed stoichiometric amounts of Zn2+ upon reaction with diacylglycerol, phorbol ester, or reactive oxygen in vitro. Our results offer new insight into the regulation of PKC. Far from cementing rigid structures, zinc actually is the linchpin that orchestrates dynamic changes in response to specific signals, allowing kinase activity to be turned on or off.

* This work was supported by American Heart Association Grant 0030397T (to I. K.) and National Institute of Health Grants CA 49933 (to U. H.) and CA 89362.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: MSKCC, Box 382, 1275 York Ave., New York, NY 10021. Tel.: 212-639-7522; Fax: 212-794-4019; E-mail:

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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