Abstract
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.
MeSH terms
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Actins / metabolism
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Animals
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Cell Movement
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Cell Surface Extensions / metabolism*
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Chemotaxis / physiology*
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Enzyme Inhibitors / pharmacology
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Imidazoles / pharmacology
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Immunoblotting
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Intracellular Signaling Peptides and Proteins
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Lipid Metabolism
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Mice
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Mice, Inbred C57BL
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Microscopy, Confocal
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Microscopy, Fluorescence
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N-Formylmethionine Leucyl-Phenylalanine / pharmacology
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Neutrophils / cytology*
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Neutrophils / metabolism
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PTEN Phosphohydrolase
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphatidylinositol Phosphates / biosynthesis
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Phosphoric Monoester Hydrolases / biosynthesis*
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Phosphorylation
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Protein Serine-Threonine Kinases / physiology*
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Pyridines / pharmacology
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Thiazoles / pharmacology
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Thiazolidines
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Time Factors
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Tumor Suppressor Proteins / biosynthesis*
Substances
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Actins
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Bridged Bicyclo Compounds, Heterocyclic
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Enzyme Inhibitors
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Imidazoles
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Intracellular Signaling Peptides and Proteins
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Phosphatidylinositol Phosphates
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Pyridines
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Thiazoles
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Thiazolidines
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Tumor Suppressor Proteins
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phosphatidylinositol 3,4,5-triphosphate
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N-Formylmethionine Leucyl-Phenylalanine
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MAP-kinase-activated kinase 2
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Protein Serine-Threonine Kinases
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase
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latrunculin B
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SB 203580