Leading the way: Directional sensing through phosphatidylinositol 3-kinase and other signaling pathways.
Chemoattractant-responsive cells are able to translate a shallow extracellular chemical gradient into a steep intracellular gradient resulting in the localization of F-actin assembly at the front and an actomyosin network at the rear that moves the cell forward. Recent evidence suggests that one of the first asymmetric cellular responses is the localized accumulation of PtdIns(3,4,5)P3, the product of class I phosphoinositide 3-kinase (PI3K) at the site of the new leading edge. The strong accumulation of PtdIns(3,4,5)P3 results from the localized activation of PI3K and also from feedback loops that amplify PtdIns(3,4,5)P3 synthesis at the front and control its degradation at the side and back of cells. These different pathways are temporally and spatially regulated and integrate with other signaling pathways during directional sensing and chemotaxis.
Merlot
Sylvain
S
Section of Cell and Developmental Biology, Division of Biological Sciences and Center for Molecular Genetics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0634, USA.
Firtel
Richard A
RA
D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity; D002633:Chemotaxis / Q000502:physiology*; D004023:Dictyostelium / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015800:Protozoan Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D000205:Actomyosin; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D015800:Protozoan Proteins; D025521:Tumor Suppressor Proteins; D020741:rho GTP-Binding Proteins; C428644:PhdA protein, Dictyostelium; C060974:phosphatidylinositol 3,4,5-triphosphate; C494929:PTEN protein, human