Journal ArticleDOI
Central role for G protein-coupled phosphoinositide 3-kinase γ in inflammation
Emilio Hirsch,Vladimir L. Katanaev,Cecilia Garlanda,Ornella Azzolino,Luciano Pirola,Lorenzo Silengo,Silvano Sozzani,Alberto Mantovani,Alberto Mantovani,Fiorella Altruda,Matthias P. Wymann +10 more
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TLDR
Results demonstrate that PI3Kγ is a crucial signaling molecule required for macrophage accumulation in inflammation and shows reduced migration toward a wide range of chemotactic stimuli and a severely defective accumulation in a septic peritonitis model.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 PI3Kgamma were viable and had fully differentiated neutrophils and macrophages. Chemoattractant-stimulated PI3Kgamma-/- neutrophils did not produce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kinase B, and displayed impaired respiratory burst and motility. Peritoneal PI3Kgamma-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 PI3Kgamma is a crucial signaling molecule required for macrophage accumulation in inflammation.read more
Citations
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The phosphatidylinositol 3-Kinase AKT pathway in human cancer.
Igor Vivanco,Charles L. Sawyers +1 more
TL;DR: Small-molecule therapeutics that block PI3K signalling might deal a severe blow to cancer cells by blocking many aspects of the tumour-cell phenotype.
Journal ArticleDOI
Targeting the phosphoinositide 3-kinase pathway in cancer.
TL;DR: The potential of and challenges for the development of therapeutic agents that target this pathway in cancer are discussed and the potential and challenges in understanding of the PI3K pathway are highlighted.
Journal ArticleDOI
Targeting PI3K signalling in cancer: opportunities, challenges and limitations.
TL;DR: The therapeutic potential of drugs targeting PI3K–Akt signalling for the treatment of cancer is discussed and the advantages and drawbacks of different treatment strategies for targeting this pathway are focused on.
Journal ArticleDOI
AKT/PKB Signaling: Navigating the Network
Brendan D. Manning,Alex Toker +1 more
TL;DR: Improved understanding of the molecular wiring of the AKT signaling network continues to make an impact that cuts across most disciplines of the biomedical sciences.
Journal ArticleDOI
PI3K pathway alterations in cancer: variations on a theme
TL Yuan,Lewis C. Cantley +1 more
TL;DR: The high frequency of phosphoinositide 3-kinase (PI3K) pathway alterations in cancer has led to a surge in the development of PI3K inhibitors and proposed treatment strategies tailored for these genetic lesions are proposed.
References
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Journal ArticleDOI
Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses
TL;DR: Evidence is presented that wortmannin, a known inhibitor of respiratory-burst activity, acts on PtdIns 3-kinase, the enzyme producing PTDInsP3 from Ptd Ins(4,5)P2, which implies that PtdinsP3 production is not a primary event triggering elongation of actin filaments in neutrophils.
Journal ArticleDOI
Role of IL-6 and Its Soluble Receptor in Induction of Chemokines and Leukocyte Recruitment
Maria Romano,Marina Sironi,Carlo Toniatti,Nadia Polentarutti,Paolo Fruscella,Pietro Ghezzi,Raffaella Faggioni,Walter Luini,Victor W.M. van Hinsbergh,Silvano Sozzani,Federico Bussolino,Valeria Poli,Gennaro Ciliberto,Alberto Mantovani,Alberto Mantovani +14 more
TL;DR: In vivo and in vitro evidence supports the concept that the IL-6 system plays an unexpected positive role in local inflammatory reactions by amplifying leukocyte recruitment.
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