Roles of PI3Ks in leukocyte chemotaxis and phagocytosis

Stephens, Len R.; Ellson, Chris D.; Hawkins, Phillip T.

doi:10.1016/s0955-0674(02)00311-3

Cited by 235 publications

(207 citation statements)

References 54 publications

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“…PI3K has been shown to play a direct role in a regulating multiple cell functions including adhesion (30), phagocytosis (31,32), phagosome biogenesis (33) and modulation of the activities of ␤2 integrin receptors (22,23). These observations made PI3K a potential candidate for regulating cross-talk between CD14 and Mac-1 in the binding and uptake of B. anthracis spores.…”

Section: Discussionmentioning

confidence: 99%

CD14-Mac-1 interactions inBacillus anthracisspore internalization by macrophages

Oliva

Turnbough

Kearney

2009

Proc. Natl. Acad. Sci. U.S.A.

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Anthrax, a potentially lethal disease of animals and humans, is caused by the Gram-positive spore-forming bacterium Bacillus anthracis. The outermost exosporium layer of B. anthracis spores contains an external hair-like nap formed by the glycoprotein BclA. Recognition of BclA by the integrin Mac-1 promotes spore uptake by professional phagocytes, resulting in the carriage of spores to sites of spore germination and bacterial growth in distant lymphoid organs. We show that CD14 binds to rhamnose residues of BclA and acts as a coreceptor for spore binding by Mac-1. In this process, CD14 induces signals involving TLR2 and PI3k that promote inside-out activation of Mac-1, thereby enhancing spore internalization by macrophages. As observed with mice lacking Mac-1, CD14 ؊/؊ mice are also more resistant than wild-type mice to infection by B. anthracis spores. Additionally, after B. anthracis spore challenge of CD14 ؊/؊ mice, interference with the CD14-mediated signaling pathways results in increased mortality. Our results show that the binding and uptake of B. anthracis spores by phagocytic cells is a dynamic process and involves multiple receptors and signaling pathways.BcLA ͉ anthrax ͉ exosporium ͉ rhamnose receptor ͉ signaling pathways

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Section: Discussionmentioning

confidence: 99%

CD14-Mac-1 interactions inBacillus anthracisspore internalization by macrophages

Oliva

Turnbough

Kearney

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Several studies have demonstrated that PI3K is required for endocytosis using the PI3K inhibitor wortmannin (reviewed in [29,30]). …”

Section: Discussionmentioning

confidence: 99%

Visualization of Ras-PI3K interaction in the endosome using BiFC

Tsutsumi¹,

Fujioka²,

Tsuda³

et al. 2009

Cellular Signalling

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“…ERK is mostly known to be involved in proliferation (Ferlin et al, 2000;Qiang et al, 2002), although several groups have stated that in some cell types it could also be involved in migration (Bonacchi et al, 2001;Delehedde et al, 2001;Tanimura et al, 2002). The PI3K/Akt pathway is said to be an antiapoptotic pathway in myeloma (Tu et al, 2000) although numerous groups have found that PI3K plays a key role in migration and gradient-sensing in other cell types (Gerszten et al, 2001;Comer and Parent, 2002;Curnock et al, 2002;Stephens et al, 2002;Weiner, 2002).…”

Section: Discussionmentioning

confidence: 99%