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Science 11 February 2000:
Vol. 287. no. 5455, pp. 1037 - 1040
DOI: 10.1126/science.287.5455.1037
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Reports

Polarization of Chemoattractant Receptor Signaling During Neutrophil Chemotaxis

Guy Servant, 1* Orion D. Weiner, 12* Paul Herzmark, 1 Tamás Balla, 3 John W. Sedat, 2 Henry R. Bourne 1dagger

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.

1 Department of Cellular and Molecular Pharmacology and
2 Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143, USA.
3 Endocrinology and Reproduction Research Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: bourne{at}cmp.ucsf.edu

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Vav Activation and Function as a Rac Guanine Nucleotide Exchange Factor in Macrophage Colony-Stimulating Factor-Induced Macrophage Chemotaxis.
V. Vedham, H. Phee, and K. M. Coggeshall (2005)
Mol. Cell. Biol. 25, 4211-4220
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Phosphoinositide-3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation.
V. Pinho, D. G. Souza, M. M. Barsante, F. P. Hamer, M. S. De Freitas, A. G. Rossi, and M. M. Teixeira (2005)
J. Leukoc. Biol. 77, 800-810
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A Dictyostelium Homologue of WASP Is Required for Polarized F-Actin Assembly during Chemotaxis.
S. A. Myers, J. W. Han, Y. Lee, R. A. Firtel, and C. Y. Chung (2005)
Mol. Biol. Cell 16, 2191-2206
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The Phosphoinositol-3-Kinase-Protein Kinase B/Akt Pathway Is Critical for Pseudomonas aeruginosa Strain PAK Internalization.
A. Kierbel, A. Gassama-Diagne, K. Mostov, and J. N. Engel (2005)
Mol. Biol. Cell 16, 2577-2585
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Protein O-GlcNAc Modulates Motility-associated Signaling Intermediates in Neutrophils.
Z. T. Kneass and R. B. Marchase (2005)
J. Biol. Chem. 280, 14579-14585
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Stable Activation of Phosphatidylinositol 3-Kinase in the T Cell Immunological Synapse Stimulates Akt Signaling to FoxO1 Nuclear Exclusion and Cell Growth Control.
S. Fabre, V. Lang, J. Harriague, A. Jobart, T. G. Unterman, A. Trautmann, and G. Bismuth (2005)
J. Immunol. 174, 4161-4171
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Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling.
W. von Stein, A. Ramrath, A. Grimm, M. Muller-Borg, and A. Wodarz (2005)
Development 132, 1675-1686
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Golgi polarization in a strong electric field.
J. Pu and M. Zhao (2005)
J. Cell Sci. 118, 1117-1128
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Ca2+-Dependent Regulation of Rho GTPases Triggers Turning of Nerve Growth Cones.
M. Jin, C.-b. Guan, Y.-a. Jiang, G. Chen, C.-t. Zhao, K. Cui, Y.-q. Song, C.-p. Wu, M.-m. Poo, and X.-b. Yuan (2005)
J. Neurosci. 25, 2338-2347
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The FWD1/{beta}-TrCP-mediated degradation pathway establishes a 'turning off switch' of a Cdc42 guanine nucleotide exchange factor, FGD1.
M. Hayakawa, H. Kitagawa, K. Miyazawa, M. Kitagawa, and K. Kikugawa (2005)
Genes Cells 10, 241-251
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