Journal
JOURNAL OF CELL SCIENCE
Volume 121, Issue 5, Pages 551-559Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.023333
Keywords
Dictyostelium; phospholipase; PTEN; phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5) P-3]; Ras; cytoskeleton
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Funding
- NIGMS NIH HHS [R01 GM037830-22, R01 GM037830, R01 GM024279, R01 GM024279-30, R01 GM084227] Funding Source: Medline
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM037830, R01GM024279] Funding Source: NIH RePORTER
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Phosphoinositide 3-kinase ( PI3K), PTEN and localized phosphatidylinositol ( 3,4,5)-trisphosphate [ PtdIns( 3,4,5) P-3] play key roles in chemotaxis, regulating cell motility by controlling the actin cytoskeleton in Dictyostelium and mammalian cells. PtdIns( 3,4,5) P3, produced by PI3K, acts via diverse downstream signaling components, including the GTPase Rac, Arf-GTPases and the kinase Akt (PKB). It has become increasingly apparent, however, that chemotaxis results from an interplay between the PI3K-PTEN pathway and other parallel pathways in Dictyostelium and mammalian Journal of Cell Science cells. In Dictyostelium, the phospholipase PLA2 acts in concert with PI3K to regulate chemotaxis, whereas phospholipase C ( PLC) plays a supporting role in modulating PI3K activity. In adenocarcinoma cells, PLC and the actin regulator cofilin seem to provide the direction-sensing machinery, whereas PI3K might regulate motility.
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