RRC ID 29041
Author Funamoto S, Meili R, Lee S, Parry L, Firtel RA.
Title Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN mediates chemotaxis.
Journal Cell
Abstract We have investigated the mechanisms of leading edge formation in chemotaxing Dictyostelium cells. We demonstrate that while phosphatidylinositol 3-kinase (PI3K) transiently translocates to the plasma membrane in response to chemoattractant stimulation and to the leading edge in chemotaxing cells, PTEN, a negative regulator of PI3K pathways, exhibits a reciprocal pattern of localization. By uniformly localizing PI3K along the plasma membrane, we show that chemotaxis pathways are activated along the lateral sides of cells and PI3K can initiate pseudopod formation, providing evidence for a direct instructional role of PI3K in leading edge formation. These findings provide evidence that differential subcellular localization and activation of PI3K and PTEN is required for proper chemotaxis.
Volume 109(5)
Pages 611-23
Published 2002-5-31
DOI 10.1016/s0092-8674(02)00755-9
PII S0092867402007559
PMID 12062104
MeSH Animals Cell Compartmentation / genetics* Cell Membrane / enzymology Cell Membrane / ultrastructure Cell Polarity / genetics* Chemotaxis / physiology* Dictyostelium / cytology Dictyostelium / enzymology* Dictyostelium / genetics Down-Regulation / physiology Green Fluorescent Proteins Indicators and Reagents / metabolism Isoenzymes / genetics Isoenzymes / metabolism Luminescent Proteins / metabolism PTEN Phosphohydrolase Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism* Phosphatidylinositols / metabolism* Phosphoric Monoester Hydrolases / genetics Phosphoric Monoester Hydrolases / metabolism* Protein Structure, Tertiary / genetics Protein Transport / genetics Protozoan Proteins / genetics Protozoan Proteins / metabolism Pseudopodia / enzymology Pseudopodia / ultrastructure Signal Transduction / physiology Time Factors Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* ras Proteins / genetics ras Proteins / metabolism
IF 38.637
Times Cited 570
Cellular slime molds S00007