Phosphatidylinositide 3-kinase localizes to cytoplasmic lipid bodies in human polymorphonuclear leukocytes and other myeloid-derived cells.
Phosphatidylinositide 3-kinase (PI3K) is a key enzyme implicated in intracellular signaling of diverse cellular responses including receptor-mediated responses and neutrophil activation. Several PI3K subunits have been cloned and shown to be localized to plasma membrane receptors, the cytosol, or intracellular vesicles or caveolae. We report the localization of PI3K to a distinct intracellular site, cytoplasmic lipid bodies, in leukocytes. In U937 monocyte cells, PI3K p85 regulatory and p110beta catalytic subunits were localized to lipid bodies by immunocytochemistry and/or immunoblotting and enzyme assays of subcellular fractions. In RAW murine macrophages, p55, p85alpha, and p85beta PI3K subunits were present at isolated lipid bodies. PI3K p85 was also shown to colocalize and, by co-immunoprecipitation, to be physically associated with phosphorylated Lyn kinase in lipid bodies induced to form in human polymorphonuclear leukocytes. These findings, therefore, indicate a novel site for PI3K compartmentalization and suggest that PI3K-mediated signaling is active within cytoplasmic lipid bodies in leukocytes.
Yu
W
W
Harvard Thorndike Laboratories and the Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Cassara
J
J
Weller
P F
PF
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology*; D019281:Dimerization; D006801:Humans; D046911:Macromolecular Substances; D008264:Macrophages / Q000201:enzymology* / Q000648:ultrastructure; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology* / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization; D013347:Subcellular Fractions / Q000201:enzymology; D020298:U937 Cells / Q000201:enzymology* / Q000648:ultrastructure; D019061:src-Family Kinases / Q000378:metabolism
D001095:Arachidonic Acids; D046911:Macromolecular Substances; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases