Syrbu S I, Waterman W H, Molski T F, Nagarkatti D, Hajjar J J, Sha'afi R I
Department of Physiology, University of Connecticut Health Center, Farmington 06030, USA.
J Immunol. 1999 Feb 15;162(4):2334-40.
Kinases mediating phosphorylation and activation of cytosolic phospholipase A2 (cPLA2) in intact cells remain to be fully characterized. Platelet-activating factor stimulation of human neutrophils increases cPLA2 phosphorylation. This increase is inhibited by PD 98059, a mitogen-activated protein (MAP)/extracellular signal-regulating kinase (erk) 1 inhibitor, but not by SB 203580, a p38 MAP kinase inhibitor, indicating that this action is mediated through activation of the p42 MAP kinase (erk2). However, platelet-activating factor-induced arachidonic acid release is inhibited by both PD 98059 and SB 203580. Stimulation by TNF-alpha increases cPLA2 phosphorylation, which is inhibited by SB 203580, but not PD 98059, suggesting a role for p38 MAP kinase. LPS increases cPLA2 phosphorylation and arachidonic acid release. However, neither of these actions is inhibited by either PD 98059 or SB 203580. PMA increases cPLA2 phosphorylation. This action is inhibited by PD 98059 but not SB 203580. Finally, FMLP increases cPLA2 phosphorylation and arachidonic acid release. Interestingly, while the FMLP-induced phosphorylation of cPLA2 is not affected by the inhibitors of the p38 MAP kinase or erk cascades, both inhibitors significantly decrease arachidonic acid release stimulated by FMLP. SB 203580 or PD 98059 has no inhibitory effects on the activity of coenzyme A-independent transacylase.
介导完整细胞中胞质磷脂酶A2（cPLA2）磷酸化和激活的激酶仍有待全面鉴定。血小板激活因子刺激人中性粒细胞会增加cPLA2磷酸化。这种增加被丝裂原活化蛋白（MAP）/细胞外信号调节激酶（erk）1抑制剂PD 98059抑制，但不被p38 MAP激酶抑制剂SB 203580抑制，表明该作用是通过p42 MAP激酶（erk2）的激活介导的。然而，血小板激活因子诱导的花生四烯酸释放被PD 98059和SB 203580均抑制。肿瘤坏死因子-α刺激会增加cPLA2磷酸化，这被SB 203580抑制，但不被PD 98059抑制，提示p38 MAP激酶发挥作用。脂多糖增加cPLA2磷酸化和花生四烯酸释放。然而，这些作用均不被PD 98059或SB 203580抑制。佛波酯增加cPLA2磷酸化。该作用被PD 98059抑制，但不被SB 203580抑制。最后，N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸增加cPLA2磷酸化和花生四烯酸释放。有趣的是，虽然N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸诱导的cPLA2磷酸化不受p38 MAP激酶或erk级联反应抑制剂的影响，但两种抑制剂均显著降低N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸刺激的花生四烯酸释放。SB 203580或PD 98059对辅酶A非依赖性转酰基酶的活性无抑制作用。
