The C1 Domain of Protein Kinase C as a Lipid Bilayer Surface Sensing Module
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- 作者：Cojen Ho ; Simon J. Slater ; Brigid Stagliano ; and Christopher D. Stubbs
- 刊名：Biochemistry
- 出版年：2001
- 出版时间：August 28, 2001
- 年：2001
- 卷：40
- 期：34
- 页码：10334 - 10341
- 全文大小：90K
- 年卷期：v.40,no.34(August 28, 2001)
- ISSN：1520-4995
文摘
The activity of membrane-associated protein kinase C (PKC) is tightly controlled by the physicalproperties of the membrane lipid bilayer, in particular, curvature stress, which is induced by bilayer-destabilizing lipid components. An important example of this is the weakened lipid headgroup interactionsinduced by phosphatidylethanolamine (PE) and cholesterol. In this work our previous observation with amixed isoform PKC showing a biphasic dependence of activity as a function of membrane curvaturestress [Slater et al. (1994) J. Biol. Chem. 269, 4866-4871] was here extended to individual isoforms.The Ca2+-dependent PKC
, PKC
, and PKC
, along with Ca2+-independent PKC
, but not PKC
orPKC
, displayed a biphasic activity as a function of membrane PE content. The fluorescence anisotropyof N-(5-dimethylaminonaphthalene-1-sulfonyl)dioleoylphosphatidylserine (dansyl-PS), which probes thelipid environment of PKC, also followed a biphasic profile as a function of PE content for full-lengthPKC, PKC
, and PKC as did the isolated C1 domain of PKC. In addition, the rotational correlationtime of both PKC and PKC C1-domain-associated sapintoxin D, a fluorescent phorbol ester, was alsoa biphasic function of membrane lipid PE content. These results indicate that the C1 domain acts as asensor of the bilayer surface properties and that its conformational response to these effects may directlyunderlie the resultant effects on enzyme activity.
, PKC, and PKC, along with Ca2+-independent PKC, but not PKC orPKC, displayed a biphasic activity as a function of membrane PE content. The fluorescence anisotropyof N-(5-dimethylaminonaphthalene-1-sulfonyl)dioleoylphosphatidylserine (dansyl-PS), which probes thelipid environment of PKC, also followed a biphasic profile as a function of PE content for full-lengthPKC, PKC, and PKC as did the isolated C1 domain of PKC. In addition, the rotational correlationtime of both PKC and PKC C1-domain-associated sapintoxin D, a fluorescent phorbol ester, was alsoa biphasic function of membrane lipid PE content. These results indicate that the C1 domain acts as asensor of the bilayer surface properties and that its conformational response to these effects may directlyunderlie the resultant effects on enzyme activity.