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Publication : Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis.

First Author  Hannigan M Year  2002
Journal  Proc Natl Acad Sci U S A Volume  99
Issue  6 Pages  3603-8
PubMed ID  11904423 Mgi Jnum  J:146418
Mgi Id  MGI:3837540 Doi  10.1073/pnas.052010699
Citation  Hannigan M, et al. (2002) Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis. Proc Natl Acad Sci U S A 99(6):3603-8
abstractText  Confocal imaging and time-lapsed videomicroscopy were used to study the directionality, motility, rate of cell movement, and morphologies of phosphoinositide 3-kinase gamma (PI3K)gamma(-/-) neutrophils undergoing chemotaxis in Zigmond chambers containing N-formyl-Met-Leu-Phe gradients. Most of the PI3Kgamma(-/-) neutrophils failed to translocate up the chemotactic gradient. A partial reduction in cell motility and abnormal morphologies were also observed. In the wild-type neutrophils, the pleckstrin homology domain-containing protein kinase B (AKT) and F-actin colocalize to the leading edge of polarized neutrophils oriented toward the gradient, which was not observed in PI3Kgamma(-/-) neutrophils. In PI3Kgamma(-/-) neutrophils, AKT staining consistently failed to perfectly overlap with the F-actin. This failure was observed as an F-actin-filled region of 2.3 +/- 0.5 microm between AKT and the cell membrane. These data suggest that PI3Kgamma regulates neutrophil chemotaxis primarily by controlling the direction of cell migration and the intracellular colocalization of AKT and F-actin to the leading edge.
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