A requirement of MAPKAPK2 in the uropod localization of PTEN during FMLP-induced neutrophil chemotaxis

Biochem Biophys Res Commun. 2004 Apr 9;316(3):666-72. doi: 10.1016/j.bbrc.2004.02.107.

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

  • Actins / metabolism
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cell Movement
  • Cell Surface Extensions / metabolism*
  • Chemotaxis / physiology*
  • Enzyme Inhibitors / pharmacology
  • Imidazoles / pharmacology
  • Immunoblotting
  • Intracellular Signaling Peptides and Proteins
  • Lipid Metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / cytology*
  • Neutrophils / metabolism
  • PTEN Phosphohydrolase
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol Phosphates / biosynthesis
  • Phosphoric Monoester Hydrolases / biosynthesis*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / physiology*
  • Pyridines / pharmacology
  • Thiazoles / pharmacology
  • Thiazolidines
  • Time Factors
  • Tumor Suppressor Proteins / biosynthesis*

Substances

  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Enzyme Inhibitors
  • Imidazoles
  • Intracellular Signaling Peptides and Proteins
  • Phosphatidylinositol Phosphates
  • Pyridines
  • Thiazoles
  • Thiazolidines
  • Tumor Suppressor Proteins
  • phosphatidylinositol 3,4,5-triphosphate
  • N-Formylmethionine Leucyl-Phenylalanine
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • latrunculin B
  • SB 203580