Phosphatidylserine affects specificity of protein kinase C substrate phosphorylation and autophosphorylation.
Phosphatidylserine affects specificity of protein kinase C substrate phosphorylation and autophosphorylation.
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DOI：
10.1021/bi00480a015
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发表时间：
1990-07
期刊：
影响因子：
2.9
通讯作者：
A. Newton;D. Koshland
中科院分区：
文献类型：
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作者：
A. Newton;D. Koshland
蛋白激酶C底物磷酸化和自磷酸化是由模型膜中的磷脂酰丝氨酸浓度差异调制。底物磷酸化和自磷酸化都显示出对由二酰基甘油和磷脂酰胆碱或细胞脂质（胆固醇、鞘磷脂、磷脂酰乙醇胺和磷脂酰胆碱）混合物组成的超声囊泡中的磷脂酰丝氨酸的合作依赖性。然而，支持磷酸化所需的磷脂酰丝氨酸的浓度因底物而异。一般来说，自磷酸化有利于在中间磷脂酰丝氨酸浓度，而底物磷酸化占主导地位，在高磷脂酰丝氨酸浓度。这些不同的磷脂酰丝氨酸依赖性可能反映了特定底物对带负电荷的膜的不同亲和力。增加超声处理的囊泡的负表面电荷增加底物磷酸化的速率。与磷脂酰丝氨酸的调节相反，甘油二酯激活蛋白激酶C同样朝向底物磷酸化和自磷酸化。这些结果表明，二酰基甘油和磷脂酰丝氨酸调节蛋白激酶C的活性在膜上：二酰基甘油打开酶，而磷脂酰丝氨酸影响对不同底物的特异性。
Protein kinase C substrate phosphorylation and autophosphorylation are differentially modulated by the phosphatidylserine concentration in model membranes. Both substrate phosphorylation and auto-phosphorylation display a cooperative dependence on phosphatidylserine in sonicated vesicles composed of diacylglycerol and either phosphatidylcholine or a mixture of cell lipids (cholesterol, sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine). However, the concentration of phosphatidylserine required to support phosphorylation varies with individual substrates. In general, autophosphorylation is favored at intermediate phosphatidylserine concentrations, while substrate phosphorylation dominates at high phosphatidylserine concentrations. These different phosphatidylserine dependencies may reflect different affinities of particular substrates for negatively charged membranes. Increasing the negative surface charge of sonicated vesicles increases the rate of substrate phosphorylation. In contrast to the modulation exerted by phosphatidylserine, diacylglycerol activates protein kinase C equally toward substrate phosphorylation and autophosphorylation. These results indicate that both diacylglycerol and phosphatidylserine regulate protein kinase C activity in the membrane: diacylglycerol turns the enzyme on, while phosphatidylserine affects the specificity toward different substrates.