Ligand-induced conformational changes in cytosolic protein kinase C

Lester, Davis S.; Brumfeld, Vlad

doi:10.1016/0141-8130(90)90005-u

Cited by 13 publications

(9 citation statements)

References 22 publications

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“…PKC activity is known to be markedly enhanced by translocation of the enzyme from an aqueous to a membrane environment [22]. In the absence of Ole2Gro, Ca2+ is required for the formation of a stable PKCphosphatidylserine complex [5]. The enzyme binds calcium in a phospholipid-dependent manner [5, 61 but this binding is not sufficient for the activation of the enzyme [23].…”

Section: Discussionmentioning

confidence: 99%

“…The enzyme binds calcium in a phospholipid-dependent manner [5, 61 but this binding is not sufficient for the activation of the enzyme [23]. Additional Caz+ is required as a cofactor for maximal enzyme activity with phosphatidylserine and for attainment of the final active conformation [5].…”

Section: Discussionmentioning

confidence: 99%

“…The phospholipid requirement for the enzyme is specific for anionic lipids with phosphatidylserine being most effective [2] but phosphatidic acid [2 -41, cardiolipin [3] and phosphatidylinositol [2] are also active. Calcium binds to PKC only in the presence of phospholipid [5] and the binding affinity for Ca2+ is increased with more phosphatidylserine in the membrane [6]. Diacylglycerols markedly increase the sensitivity of PKC to activation by Ca2+ in the presence of phospholipid [7].…”

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confidence: 99%

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Lipid vesicles which can bind to protein kinase C and activate the enzyme in the presence of EGTA

Epand

Stafford

Lester

1992

European Journal of Biochemistry

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Maximal protein kinase C activity with vesicles of phosphatidic acid and 1,2-di0leoyl-~sn-glycerol is observed in the absence of added Ca2 '. Addition of phosphatidylcholine to these vesicles restores some calcium dependence of enzyme activity. 1,2-Dioleoyl-sn-glycerol eliminates the Ca2 +-dependence of protein kinase C activity found with phosphatidic acid alone. Phorbol esters do not mimic the action of 1,2-dioleoyl-sn-glyceroI in this respect. This suggests that the 1,2-dioleoyl-sn-glycerol effect is a result of changes it causes in the physical properties of the membrane rather than to specific binding to the enzyme. The effect of 1,2-dioleoyl-.~n-glycerol on the phosphatidic-acid-stimulated protein kinase C activity is dependent on the molar Craction of 1,2-dioleoyl-sn-glycerol used and results in a gradual shift from Ca2+ stimulation at low 1,2-dioleoyl-sn-glycerol concentrations to calcium inhibition at higher concentrations of 1,2-dioleoyl-sn-glycerol. Phosphatidylserine-stimulated activity is also shown to be largely independent of the calcium concentration at higher molar fractions of 1,2-dioleoyl-sn-glycerol. Thus, with certain lipid compositions, protein kinase C activity becomes independent of the calcium concentration or requires only very low, stoichiometric binding of Ca2 + to high affinity sites on the enzyme.Protein kinase C can bind to phosphatidic acid vesicles more readily than it can bind to phosphatidylserine vesicles in the absence of calcium. Addition of 1,2-dioleoyl-sn-glycerol to phosphatidylserine vesicles promotes the partitioning of protein kinase C into the membrane in the absence of added Ca2 ' . There is no isozyme specificity in this binding. These results suggest that a less-tightly packed headgroup region of the bilayer causes increased insertion of protein kinase C into the membrane. This is a necessary but not sufficient condition for activation of the enzyme in the presence of EGTA.Protein kinase C (PKC) plays an important role in cell regulation and is the receptor for the phorbol ester tumor promoters. This protein kinase was first identified as a calcium-dependent and phospholipid-dependent enzyme [ l]. The phospholipid requirement for the enzyme is specific for anionic lipids with phosphatidylserine being most effective [2] but phosphatidic acid [2 -41, cardiolipin [3] and phosphatidylinositol [2] are also active. Calcium binds to PKC only in the presence of phospholipid [5] and the binding affinity for Ca2+ is increased with more phosphatidylserine in the membrane [6]. Diacylglycerols markedly increase the sensitivity of PKC to activation by Ca2+ in the presence of phospholipid [7]. In contrast to phosphatidylserine, we find that addition of 1,2-dioleoyl-sn-glycerol (Ole,Gro) to phosphatidic acid causes a calcium-induced inhibition, rather than activation, of the Correspondence to

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Lipid vesicles which can bind to protein kinase C and activate the enzyme in the presence of EGTA

Epand

Stafford

Lester

1992

European Journal of Biochemistry

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“…However, recent examination of several ATPrequiring enzymes has forced a re-examination of this assumption. A Mg# + -binding pocket has been described for protein kinase C [10][11][12]. When this site is occupied by Mg# + , the conformation and catalytic activity of the protein change [12].…”

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confidence: 99%

“…A Mg# + -binding pocket has been described for protein kinase C [10][11][12]. When this site is occupied by Mg# + , the conformation and catalytic activity of the protein change [12]. In a similar fashion, calmodulin-dependent protein kinase [13] and insulin-dependent tyrosine kinase [14] also have a requirement for Mg# + , which appears to be separate from the requirement for MgATP.…”

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confidence: 99%

Evidence for a single non-arachidonic acid-specific fatty acyl-CoA synthetase in heart which is regulated by Mg2+

Saunders

Voigt

Weis

1996

Biochemical Journal

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Previous reports indicated that arachidonic acid is incorporated into the isolated perfused rabbit heart in preference to other fatty acids, and that incorporation of arachidonic acid, but not other fatty acids, is inhibited during Mg2+ depletion. In this study, we have not been able to demonstrate an arachidonic acid-specific fatty acyl-CoA synthetase in rat or rabbit heart by hydroxyapatite chromatography. Kinetic evidence was consistent with a single enzyme, as the slopes of pseudo-Hill plots were not significantly different from -1. The single fatty acyl-CoA synthetase present appears to prefer C18:0 unsaturated fatty acids to arachidonate, and had about the same affinity for C10:0 -C14:0 saturated fatty acids as for arachidonate. At 35 microM arachidonate, enzyme velocity increased as the total Mg2+ was increased from 3 to 80 mM. Calculated [MgATP] indicated that the MgATP complex was not rate-limiting. At low concentrations, Mn2+ and Ni2+ supported activity, but Cu2+ and Zn2+ did not. Low Ca2+ concentrations activated only oleic acid conversion. Kinetic analysis indicated that the Vmax of the enzyme was increased with increasing concentrations of ionized Mg2+ for both oleic acid and arachidonic acid. The data are constant with the hypothesis that Mg2+ has a direct effect on fatty acyl-CoA synthetase activity, and suggest that preference for oleic acid and arachidonic acid can be influenced by the ionic milieu.

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Lateralization of membrane-associated protein kinase C in rat piriform cortex: Specific to operant training cues in the olfactory modality

Olds

Bhalla

McPhie

et al. 1994

Behavioural Brain Research

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Ligand-induced conformational changes in cytosolic protein kinase C

Cited by 13 publications

References 22 publications

Lipid vesicles which can bind to protein kinase C and activate the enzyme in the presence of EGTA

Lipid vesicles which can bind to protein kinase C and activate the enzyme in the presence of EGTA

Evidence for a single non-arachidonic acid-specific fatty acyl-CoA synthetase in heart which is regulated by Mg2+

Lateralization of membrane-associated protein kinase C in rat piriform cortex: Specific to operant training cues in the olfactory modality

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