RRC ID 29028
Author Chung CY, Potikyan G, Firtel RA.
Title Control of cell polarity and chemotaxis by Akt/PKB and PI3 kinase through the regulation of PAKa.
Journal Mol Cell
Abstract We demonstrate that PI3 kinase and protein kinase B (PKB or Akt) control cell polarity and chemotaxis, in part, through the regulation of PAKa, which is required for myosin II assembly. We demonstrate that PI3K and PKB mediate PAKa's subcellular localization, PAKa's activation in response to chemoattractant stimulation, and chemoattractant-mediated myosin II assembly. Mutation of the PKB phosphorylation site in PAKa to Ala blocks PAKa's activation and inhibits PAKa redistribution in response to chemoattractant stimulation, whereas an Asp substitution leads to an activated protein. Addition of the PI3K inhibitor LY294002 results in a rapid loss of cell polarity and the axial distribution of actin, myosin, and PAKa. These results provide a mechanism by which PI3K regulates chemotaxis.
Volume 7(5)
Pages 937-47
Published 2001-5-1
DOI 10.1016/s1097-2765(01)00247-7
PII S1097-2765(01)00247-7
PMID 11389841
MeSH Animals Cell Polarity / drug effects* Chemotaxis / drug effects* Cytoskeletal Proteins / drug effects Cytoskeletal Proteins / physiology Dictyostelium / cytology Dictyostelium / genetics Dictyostelium / physiology Enzyme Activation / drug effects Enzyme Activation / genetics Mutagenesis, Site-Directed Phosphatidylinositol 3-Kinases / pharmacology* Phosphatidylinositol 3-Kinases / physiology Phosphorylation Protein-Serine-Threonine Kinases / drug effects* Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism Proto-Oncogene Proteins / pharmacology* Proto-Oncogene Proteins / physiology Proto-Oncogene Proteins c-akt Signal Transduction / drug effects Signal Transduction / physiology Subcellular Fractions / drug effects Subcellular Fractions / physiology Transfection
IF 15.584
Times Cited 160
Cellular slime molds S00007 S00335