Polarization of chemoattractant receptor signaling during neutrophil chemotaxis.
Morphologic polarity is necessary for chemotaxis of mammalian cells. As a probe of intracellular signals responsible for this asymmetry, the pleckstrin homology domain of the AKT protein kinase (or protein kinase B), tagged with the green fluorescent protein (PHAKT-GFP), was expressed in neutrophils. Upon exposure of cells to chemoattractant, PHAKT-GFP is recruited selectively to membrane at the cell's leading edge, indicating an internal signaling gradient that is much steeper than that of the chemoattractant. Translocation of PHAKT-GFP is inhibited by toxin-B from Clostridium difficile, indicating that it requires activity of one or more Rho guanosine triphosphatases.
Servant
G
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Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94143, USA.
Weiner
O D
OD
Herzmark
P
P
Balla
T
T
Sedat
J W
JW
Bourne
H R
HR
D000199:Actins / Q000378:metabolism; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D016764:Cell Polarity; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D015936:Complement C5a / Q000494:pharmacology; D003593:Cytoplasm / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011554:Pseudopodia / Q000201:enzymology; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D000199:Actins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002630:Chemotactic Factors; D002867:Chromones; D015936:Complement C5a; D004791:Enzyme Inhibitors; D007328:Insulin; D009025:Morpholines; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; D020741:rho GTP-Binding Proteins; C031815:toxB protein, Clostridium difficile; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494918:AKT1 protein, human