Differential activation of protein kinase C isozymes by short chain phosphatidylserines and phosphatidylcholines.

Walker, J M; Homan, Elizabeth; Sando, Julianne J.

doi:10.1016/s0021-9258(19)39032-5

Cited by 60 publications

(10 citation statements)

References 28 publications

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“…Also, it was reported that PKCβ (I or II) differs from PKCR in containing only a single class of low-affinity Gd 3+ -binding sites, consistent with the observation in this study that the Ca 2+induced increase in RET for PKCβI was monophasic. This difference between PKCR and PKCβ (I or II) was also observed in another study where the activities of both isoforms, induced in the presence of short chain phospholipid micelles, were entirely Ca 2+ -and phospholipid-dependent, while PKCR was shown to have an extra Ca 2+ requirement that did not involve phospholipid interactions (54). However, the stoichiometry of Ca 2+ binding to PKCβI remains unclear.…”

Section: Discussionsupporting

confidence: 61%

Synergistic Activation of Protein Kinase Cα, -βI, and -γ Isoforms Induced by Diacylglycerol and Phorbol Ester: Roles of Membrane Association and Activating Conformational Changes

et al. 1999

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Protein kinase Calpha (PKCalpha) has been shown to contain two discrete activator sites with differing binding affinities for phorbol esters and diacylglycerols. The interaction of diacylglycerol with a low-affinity phorbol ester binding site leads to enhanced high-affinity phorbol ester binding and to a potentiated level of activity [Slater, S. J., Ho, C., Kelly, M. B., Larkin, J. D. , Taddeo, F. J., Yeager, M. D., and Stubbs, C. D. (1996) J. Biol. Chem. 271, 4627-4631]. In this study, the mechanism of this enhancement of activity was examined with respect to the Ca2+ dependences of membrane association and accompanying conformational changes that lead to activation. The association of PKCalpha with membranes containing 12-O-tetradecanoylphorbol 13-acetate (TPA) or 1, 2-dioleoylglycerol (DAG), determined from tryptophan to dansyl-PE resonance energy transfer (RET) measurements, was found to occur at relatively low Ca2+ levels (

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Section: Discussionsupporting

confidence: 61%

Synergistic Activation of Protein Kinase Cα, -βI, and -γ Isoforms Induced by Diacylglycerol and Phorbol Ester: Roles of Membrane Association and Activating Conformational Changes

et al. 1999

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“…We speculate that PKC activation at domain interfaces may share features with activation by short-chain PC micelles (Walker et al, 1990;Walker & Sando, 1988), by highly unsaturated phospholipids (Bolen & Sando, 1992) in the presence of DO, and by branched-chain analogues of distearin (DS) with bulky derivatives (Zhou et al, 1988). Short-chain PC micelles have a spacing between the lipid components more similar to a monolayer in the liquidextended phase than to a bilayer (McConnell, 1991).…”

Section: Discussionmentioning

confidence: 99%

Activation of Protein Kinase C by Coexisting Diacylglycerol-Enriched and Diacylglycerol-Poor Lipid Domains

et al. 1997

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To test the hypothesis that activation of protein kinase C (PKC) is related to the interface between coexisting diacylglycerol- (DAG-) enriched and DAG-poor phases, the thermotropic phase behavior of the ternary mixtures dimyristoylphosphatidylcholine (DMPC)/dimyristoylphosphatidylserine (DMPS)/dioleoylglycerol (DO), DMPC/DMPS/1-palmitoyl-2-oleoylglycerol (PO), and DMPC/DMPS/dimyristoylglycerol (DM) was analyzed and compared with the ability of the lipid mixtures to support PKC activity. Differential scanning calorimetry (DSC) was used to monitor the gel-to-liquid crystalline phase transition as a function of the mole fraction of DO (chiDO), PO (chiPO), or DM (chiDM) in DMPC/DMPS (1:1) multilamellar vesicles (MLVs) and of chiDO in large unilamellar vesicles (LUVs). The addition of DAG at low mole fractions gave rise to the appearance of two or more overlapping transitions. The phase boundaries of the ternary mixtures deduced from the partial phase diagrams were chiDO = approximately 0.10 and approximately 0.3 for DMPC/DMPS/DO, chiPO = approximately 0.05 and approximately 0.4 for DMPC/DMPS/PO, and chiDM = approximately 0.025 and approximately 0.5-0.6 for DMPC/ DMPS/DM. Above these mole fractions of DAG, the transitions again became very sharp. The ability of the lipid mixtures to support activity of PKC alpha and PKC eta was examined below and above the gel-to-liquid crystalline phase transition. In the gel phase, PKC activity went through a maximum as a function of increasing mole fraction of each DAG and was restricted to lipid compositions in which coexisting phases were observed. Maximal activity decreased with increasing saturation of the DAG. In the fluid state, maximal PKC activity was shifted to higher DO mole fractions and the peak was much broader. Collectively, these data support a role for both the presence and nature of interface between compositionally distinct domains in activation of PKC.

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“…This mechanism for PKC-membrane binding does not involve Ca2+ but still features a charge interaction at the membrane surface. We have shown, however, that PC micelles, which do not bind Ca2+, can activate PKC in the absence of acidic phospholipids (Walker & Sando, 1988;Walker et al, 1990). Therefore, depending on the physical state of the lipid, charge interactions are not strictly required for activation.…”

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confidence: 90%

Effect of phospholipid unsaturation on protein kinase C activation

Bolen¹,

Sando²

1992

Biochemistry

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To examine the hypothesis that physical features of the membrane contribute to protein kinase C activation, phosphatidylcholine/phosphatidylserine/diolein (70:25:5) vesicles of defined acyl chain composition were tested for their ability to activate the enzyme. Maximal activation was found to correlate with the mole percent unsaturation in the system. Unsaturation could be provided by either the phosphatidylserine or the phosphatidylcholine component. Vesicles containing 5 mol% diolein but lacking any unsaturation in the phospholipid did not support activity, indicating that acidic head groups alone are not sufficient for activity. The saturated lipid vesicles could be rendered effective but only at very high (25 mol%) concentrations of diolein. The degree of acyl chain unsaturation and the positioning of the double bond had little effect on the activity, suggesting that the effect of the unsaturation is due to some physical property of the lipid rather than to a specific lipid-protein interaction. Addition of cholesterol to both saturated and unsaturated systems indicated that fluidity, as assessed by fluorescence anisotropy, did not correlate with activity. These results suggest that a physical property of the membrane other than fluidity is important for the activation of protein kinase C. A model for protein kinase C activation involving phase separation and/or head group spacing is discussed.

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Differential activation of protein kinase C isozymes by short chain phosphatidylserines and phosphatidylcholines.

Cited by 60 publications

References 28 publications

Synergistic Activation of Protein Kinase Cα, -βI, and -γ Isoforms Induced by Diacylglycerol and Phorbol Ester: Roles of Membrane Association and Activating Conformational Changes

Synergistic Activation of Protein Kinase Cα, -βI, and -γ Isoforms Induced by Diacylglycerol and Phorbol Ester: Roles of Membrane Association and Activating Conformational Changes

Activation of Protein Kinase C by Coexisting Diacylglycerol-Enriched and Diacylglycerol-Poor Lipid Domains

Effect of phospholipid unsaturation on protein kinase C activation

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