在FMLP诱导的中性粒细胞趋化过程中，MAPKAPK2对PTEN在尾足定位中的需求。
A requirement of MAPKAPK2 in the uropod localization of PTEN during FMLP-induced neutrophil chemotaxis.
作者信息
Wu Yue, Hannigan Michael O, Kotlyarov Alexey, Gaestel Matthias, Wu Dianqing, Huang Chi-Kuang
机构信息
Department of Pathology, University of Connecticut, Farmington, CT, USA.
出版信息
Biochem Biophys Res Commun. 2004 Apr 9;316(3):666-72. doi: 10.1016/j.bbrc.2004.02.107.
The directionality control in chemotaxis is the result of a reciprocal regulation of PI3-kinase and PTEN subcellular localization. MK2(-/-) neutrophils have a directionality loss in fMLP-induced chemotaxis. We found that in polarized WT neutrophils PTEN was localized in the uropod region. However, MK2(-/-) neutrophils or p38 MAPK inhibitor-SB203580-pretreated WT neutrophils showed a disrupted PTEN subcellular localization. Some PTEN was localized at the leading edge of the polarized neutrophils, which may lower the concentration of PI3-kinase lipid product PtdIns(3,4,5)P3 required for directionality sensing. FMLP-stimulated MK2(-/-) neutrophils or SB203580-pretreated WT neutrophils also had disrupted F-actin polarization. F-actin polymerization inhibitor lantrunculin-B disrupted the polarization of PTEN, but not PtdIns(3,4,5)P3. The results suggest that PTEN uropod polarization is F-actin polymerization-dependent and may be through the effect of MK2 on F-actin polarization.
趋化作用中的方向性控制是PI3激酶和PTEN亚细胞定位相互调节的结果。MK2基因敲除的中性粒细胞在fMLP诱导的趋化作用中出现方向性丧失。我们发现，在极化的野生型中性粒细胞中，PTEN定位于尾足区域。然而，MK2基因敲除的中性粒细胞或经p38丝裂原活化蛋白激酶抑制剂SB203580预处理的野生型中性粒细胞显示PTEN亚细胞定位紊乱。一些PTEN定位于极化中性粒细胞的前沿，这可能会降低方向性感知所需的PI3激酶脂质产物PtdIns(3,4,5)P3的浓度。fMLP刺激的MK2基因敲除的中性粒细胞或经SB203580预处理的野生型中性粒细胞也有F-肌动蛋白极化紊乱。F-肌动蛋白聚合抑制剂兰肽霉素-B破坏了PTEN的极化，但没有破坏PtdIns(3,4,5)P3的极化。结果表明，PTEN尾足极化依赖于F-肌动蛋白聚合，可能是通过MK2对F-肌动蛋白极化的作用实现的。
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