Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation
作者： Emilio Hirsch , Vladimir L Katanaev , Cecilia Garlanda , Ornella Azzolino , Luciano Pirola
DOI: 10.1126/SCIENCE.287.5455.1049
关键词: G protein 、 Protein kinase B 、 Heterotrimeric G protein 、 Signal transduction 、 Binding protein 、 Inflammation 、 Biology 、 Protein kinase A 、 Phosphoinositide 3-kinase 、 Molecular biology
摘要: Phosphoinositide 3-kinase (PI3K) activity is crucial for leukocyte function, but the roles of four receptor-activated isoforms are unclear. Mice lacking heterotrimeric guanine nucleotide-binding protein (G protein)–coupled PI3Kγ were viable and had fully differentiated neutrophils macrophages. Chemoattractant-stimulated PI3Kγ−/− did not produce phosphatidylinositol 3,4,5-trisphosphate, activate kinase B, displayed impaired respiratory burst motility. Peritoneal PI3Kγ-null macrophages showed a reduced migration toward wide range chemotactic stimuli severely defective accumulation in septic peritonitis model. These results demonstrate that signaling molecule required macrophage inflammation.
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