磷脂酸
激活剂(遗传学)
磷酸二酯酶
PLD2型
酶激活剂
磷酸二酯酶3
角色扮演
生物化学
磷脂酶D
二酰甘油激酶
第二信使系统
刺激
磷酸化
信号转导
基因亚型
酶
蛋白激酶A
化学
生物
蛋白激酶C
内分泌学
受体
磷脂
基因
膜
作者
Georges Némoz,Claudio Sette,Marco Conti
出处
期刊:Molecular Pharmacology
[American Society for Pharmacology & Experimental Therapeutics]
日期:1997-02-01
卷期号:51 (2): 242-249
被引量:57
摘要
In rat thymic lymphocytes, accumulation of phosphatidic acid (PA) occurs at the same time as decrease in cAMP levels and activation of a cAMP-specific phosphodiesterase (PDE) [type 4, EC 3.1.4.17 (PDE4)]. We investigated the nature of the PDE activated by PA and the mechanism of activation by using recombinant cAMP-specific PDE4 isoforms derived from three different genes (PDE4A, PDE4B, andPDE4D). The “long” variants expressed from each gene (PDE4A5, PDE4B1, and PDE4D3) were activated by PA, whereas the “short” variants (PDE4A1, PDE4B2, PDE4D1, and PDE4D2) were not. Phosphatidylserine was an activator that was as effective as PA, whereas phosphatidylcholine was ineffective, indicating that activation was restricted to anionic phospholipids. PA caused an increase in theVmax value of PDE4D3 without affecting theKm value of the enzyme for the cAMP substrate. PA also caused a change in the Mg2+requirement for hydrolysis. Half-maximal stimulation of the PDE was obtained with ∼10 μg/ml PA. Although protein kinase A-mediated phosphorylation of PDE4D3 produces effects similar to those elicited by PA, the mechanism of PA-induced activation was not found to involve a phosphorylation. Instead, several observations suggest that PA may directly interact with the enzyme. The stimulation of cAMP PDEs by PA and other acidic phospholipids may be a mechanism by which growth factors and hormones modulate the cAMP-dependent signal transduction pathway during cell stimulation.
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