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Science 287 (5455): 1037-1040

Copyright © 2000 by the American Association for the Advancement of Science

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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Y. J. Cho, J. M. Cunnick, S.-J. Yi, V. Kaartinen, J. Groffen, and N. Heisterkamp (2007)
Mol. Cell. Biol. 27, 899-911
   Abstract »    Full Text »    PDF »
Orchestration of lymphocyte chemotaxis by mitochondrial dynamics.
S. Campello, R. A. Lacalle, M. Bettella, S. Manes, L. Scorrano, and A. Viola (2006)
J. Exp. Med. 203, 2879-2886
   Abstract »    Full Text »    PDF »
ATP Release Guides Neutrophil Chemotaxis via P2Y2 and A3 Receptors.
Y. Chen, R. Corriden, Y. Inoue, L. Yip, N. Hashiguchi, A. Zinkernagel, V. Nizet, P. A. Insel, and W. G. Junger (2006)
Science 314, 1792-1795
   Abstract »    Full Text »    PDF »
The IL Sequence in the LLKIL Motif in CXCR2 Is Required for Full Ligand-induced Activation of Erk, Akt, and Chemotaxis in HL60 Cells.
J. Sai, G. Walker, J. Wikswo, and A. Richmond (2006)
J. Biol. Chem. 281, 35931-35941
   Abstract »    Full Text »    PDF »
Opposing Roles for Akt1 and Akt2 in Rac/Pak Signaling and Cell Migration.
G.-L. Zhou, D. F. Tucker, S. S. Bae, K. Bhatheja, M. J. Birnbaum, and J. Field (2006)
J. Biol. Chem. 281, 36443-36453
   Abstract »    Full Text »    PDF »
Role of RacC for the Regulation of WASP and Phosphatidylinositol 3-Kinase during Chemotaxis of Dictyostelium.
J. W. Han, L. Leeper, F. Rivero, and C. Y. Chung (2006)
J. Biol. Chem. 281, 35224-35234
   Abstract »    Full Text »    PDF »
DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis.
Y. Kunisaki, A. Nishikimi, Y. Tanaka, R. Takii, M. Noda, A. Inayoshi, K.-i. Watanabe, F. Sanematsu, T. Sasazuki, T. Sasaki, et al. (2006)
J. Cell Biol. 174, 647-652
   Abstract »    Full Text »    PDF »

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