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Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation
Abstract
Phosphoinositide 3-kinase (PI3K) activity is crucial for leukocyte function, but the roles of the four receptor-activated isoforms are unclear. Mice lacking heterotrimeric guanine nucleotide-binding protein (G protein)–coupled PI3Kγ were viable and had fully differentiated neutrophils and macrophages. Chemoattractant-stimulated PI3Kγ −/− neutrophils did not produce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kinase B, and displayed impaired respiratory burst and motility. Peritoneal PI3Kγ-null macrophages showed a reduced migration toward a wide range of chemotactic stimuli and a severely defective accumulation in a septic peritonitis model. These results demonstrate that PI3Kγ is a crucial signaling molecule required for macrophage accumulation in inflammation.
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Citations
Cited by
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Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772
Targeting PI3K signalling in cancer: opportunities, challenges and limitations
Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445
PI3K pathway alterations in cancer: variations on a theme
Yuan, T. L., & Cantley, L. C. (2008) · Oncogene · doi:10.1038/onc.2008.245 · Cited by 1,845
The emerging mechanisms of isoform-specific PI3K signalling
Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., & Bilanges, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2882 · Cited by 1,767
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Balla, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00028.2012 · Cited by 1,638
Metadata
- Authors
- Hirsch, E., Katanaev, V. L., Garlanda, C., Azzolino, O., Pirola, L., Silengo, L., Sozzani, S., Mantovani, A., Altruda, F., & Wymann, M. P.
- Venue
- Science
- Published
- 2000-02-11
- Volume
- 287
- Issue
- 5455
- Pages
- 1049-1053
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2061440101
- Cited by
- 1,209
- References
- 0
- FWCI
- 26.14
- Type
- journal article
- Language
- en
- Open access
- closed
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- Hirsch, E., Katanaev, V. L., Garlanda, C., Azzolino, O., Pirola, L., Silengo, L., Sozzani, S., Mantovani, A., Altruda, F., & Wymann, M. P. (2000). Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation. Science. https://doi.org/10.1126/science.287.5455.1049
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