Zinc release from protein kinase C as the common event during activation by lipid second messenger or reactive oxygen Journal Article

  


Authors: Korichneva, I.; Hoyos, B.; Chua, R.; Levi, E.; Hammerling, U.
Article Title: Zinc release from protein kinase C as the common event during activation by lipid second messenger or reactive oxygen
Abstract: 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 PKCĪ± 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.
Keywords: signal transduction; controlled study; nonhuman; protein domain; proteins; animal cell; mouse; animals; mice; cells, cultured; microscopy, confocal; lipid; molecular dynamics; cell line; transcription factor; enzyme activation; dose-response relationship, drug; enzyme activity; time factors; animalia; regulatory mechanism; reactive oxygen species; reactive oxygen metabolite; protein structure, tertiary; protein kinase c; lipids; hydrogen peroxide; enzyme kinetics; zinc; zinc finger protein; lipid metabolism; oxidation; diacylglycerol; phorbol esters; phorbol ester; 3t3 cells; stoichiometry; second messenger; zinc fingers; insects; ions; priority journal; article; lipid second messengers
Journal Title: Journal of Biological Chemistry
Volume: 277
Issue: 46
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2002-11-15
Start Page: 44327
End Page: 44331
Language: English
DOI: 10.1074/jbc.M205634200
PUBMED: 12213816
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0037113925&partnerID=40&md5=1b7a2fc45bca892c556ef7261faf6eb2
Notes: Export Date: 14 November 2014 -- Source: Scopus
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MSK Authors
  1. Irina Koritchneva
    10 Koritchneva
  2. Beatrice E Hoyos
    23 Hoyos
  3. Ramon Chua
    21 Chua
  4. Ulrich Hammerling
    79 Hammerling
  5. Ester Levi
    17 Levi
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