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Science 11 February 2000:
Vol. 287. no. 5455, pp. 1046 - 1049
DOI: 10.1126/science.287.5455.1046
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Reports

Roles of PLC-beta 2 and -beta 3 and PI3Kgamma in Chemoattractant-Mediated Signal Transduction

Zhong Li, 12* Huiping Jiang, 1*dagger Wei Xie, 1* Zuchuan Zhang, 1 Alan V. Smrcka, 1 Dianqing Wu 12ddagger

The roles of phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC) in chemoattractant-elicited responses were studied in mice lacking these key enzymes. PI3Kgamma was required for chemoattractant-induced production of phosphatidylinositol 3,4,5-trisphosphate [PtdIns (3,4,5)P3] and has an important role in chemoattractant-induced superoxide production and chemotaxis in mouse neutrophils and in production of T cell-independent antigen-specific antibodies composed of the immunoglobulin lambda  light chain (TI-Iglambda L). The study of the mice lacking PLC-beta 2 and -beta 3 revealed that the PLC pathways have an important role in chemoattractant-mediated production of superoxide and regulation of protein kinases, but not chemotaxis. The PLC pathways also appear to inhibit the chemotactic activity induced by certain chemoattractants and to suppress TI-Iglambda L production.

1 Department of Pharmacology, University of Rochester, Rochester, NY 14642, USA.
2 Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
*   These authors contributed equally to this work.

dagger    Present address: Department of Pharmacology, Boehringer Inglheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.

ddagger    To whom correspondence should be addressed. E-mail: dwu{at}neuron.uchc.edu

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Activation of Phosphoinositide 3-Kinases by the CCR4 Ligand Macrophage-Derived Chemokine Is a Dispensable Signal for T Lymphocyte Chemotaxis.
D. G. Cronshaw, C. Owen, Z. Brown, and S. G. Ward (2004)
J. Immunol. 172, 7761-7770
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Experimental Evidence for the Limiting Role of Enzymatic Reactions in Chemoattractant-induced Pseudopod Extension in Human Neutrophils.
D. Chodniewicz, A. M. Alteraifi, and D. V. Zhelev (2004)
J. Biol. Chem. 279, 24460-24466
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Distinct Transcriptional Programs Activated by Interleukin-10 with or without Lipopolysaccharide in Dendritic Cells: Induction of the B Cell-Activating Chemokine, CXC Chemokine Ligand 13.
P. Perrier, F. O. Martinez, M. Locati, G. Bianchi, M. Nebuloni, G. Vago, F. Bazzoni, S. Sozzani, P. Allavena, and A. Mantovani (2004)
J. Immunol. 172, 7031-7042
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In Vivo Activity of a Phospholipase C Inhibitor, 1-(6-((17{beta}-3-Methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), in Acute and Chronic Inflammatory Reactions.
C. Hou, T. Kirchner, M. Singer, M. Matheis, D. Argentieri, and D. Cavender (2004)
J. Pharmacol. Exp. Ther. 309, 697-704
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Mechanisms and implications of phosphoinositide 3-kinase {delta} in promoting neutrophil trafficking into inflamed tissue.
K. D. Puri, T. A. Doggett, J. Douangpanya, Y. Hou, W. T. Tino, T. Wilson, T. Graf, E. Clayton, M. Turner, J. S. Hayflick, et al. (2004)
Blood 103, 3448-3456
   Abstract »    Full Text »    PDF »
Unique SDF-1-induced activation of human precursor-B ALL cells as a result of altered CXCR4 expression and signaling.
A. Spiegel, O. Kollet, A. Peled, L. Abel, A. Nagler, B. Bielorai, G. Rechavi, J. Vormoor, and T. Lapidot (2004)
Blood 103, 2900-2907
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Lysophosphatidic Acid Induces Chemotaxis, Oxygen Radical Production, CD11b Up-Regulation, Ca2+ Mobilization, and Actin Reorganization in Human Eosinophils via Pertussis Toxin-Sensitive G Proteins.
M. Idzko, M. Laut, E. Panther, S. Sorichter, T. Durk, J. W. Fluhr, Y. Herouy, M. Mockenhaupt, D. Myrtek, P. Elsner, et al. (2004)
J. Immunol. 172, 4480-4485
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Rap1-mediated Lymphocyte Function-associated Antigen-1 Activation by the T Cell Antigen Receptor Is Dependent on Phospholipase C-{gamma}1.
K. Katagiri, M. Shimonaka, and T. Kinashi (2004)
J. Biol. Chem. 279, 11875-11881
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Modulation of bone marrow-derived neutrophil signaling by H2O2: disparate effects on kinases, NF-{kappa}B, and cytokine expression.
D. Strassheim, K. Asehnoune, J.-S. Park, J.-Y. Kim, Q. He, D. Richter, S. Mitra, J. Arcaroli, K. Kuhn, and E. Abraham (2004)
Am J Physiol Cell Physiol 286, C683-C692
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CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2.
E. Scandella, Y. Men, D. F. Legler, S. Gillessen, L. Prikler, B. Ludewig, and M. Groettrup (2004)
Blood 103, 1595-1601
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From the Cover: Analysis of C5a-mediated chemotaxis by lentiviral delivery of small interfering RNA.
J.-I. Hwang, I. D. C. Fraser, S. Choi, X.-F. Qin, and M. I. Simon (2004)
PNAS 101, 488-493
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Regulation of Leukocyte Transmigration: Cell Surface Interactions and Signaling Events.
Y. Liu, S. K. Shaw, S. Ma, L. Yang, F. W. Luscinskas, and C. A. Parkos (2004)
J. Immunol. 172, 7-13
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Differential Activation of Formyl Peptide Receptor-Like 1 by Peptide Ligands.
Y.-S. Bae, H. J. Yi, H.-Y. Lee, E. J. Jo, J. I. Kim, T. G. Lee, R. D. Ye, J.-Y. Kwak, and S. H. Ryu (2003)
J. Immunol. 171, 6807-6813
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Granulocyte-Macrophage Colony-Stimulating Factor Is a Chemoattractant Cytokine for Human Neutrophils: Involvement of the Ribosomal p70 S6 Kinase Signaling Pathway.
J. Gomez-Cambronero, J. Horn, C. C. Paul, and M. A. Baumann (2003)
J. Immunol. 171, 6846-6855
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Two Phases of Actin Polymerization Display Different Dependencies on PI(3,4,5)P3 Accumulation and Have Unique Roles during Chemotaxis.
L. Chen, C. Janetopoulos, Y. E. Huang, M. Iijima, J. Borleis, and P. N. Devreotes (2003)
Mol. Biol. Cell 14, 5028-5037
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Phosphoinositide 3-kinase {gamma}-deficient hearts are protected from the PAF-dependent depression of cardiac contractility.
G. Alloatti, R. Levi, D. Malan, L. Del Sorbo, O. Bosco, L. Barberis, A. Marcantoni, I. Bedendi, C. Penna, O. Azzolino, et al. (2003)
Cardiovasc Res 60, 242-249
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Dual Phosphorylation of Phosphoinositide 3-Kinase Adaptor Grb2-Associated Binder 2 Is Responsible for Superoxide Formation Synergistically Stimulated by Fc{gamma} and Formyl-Methionyl-Leucyl-Phenylalanine Receptors in Differentiated THP-1 Cells.
H. Momose, H. Kurosu, N. Tsujimoto, K. Kontani, K. Tsujita, H. Nishina, and T. Katada (2003)
J. Immunol. 171, 4227-4234
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Activation of Group IV Cytosolic Phospholipase A2 in Human Eosinophils by Phosphoinositide 3-Kinase Through a Mitogen-Activated Protein Kinase-Independent Pathway.
S. Myou, A. R. Leff, S. Myo, E. Boetticher, A. Y. Meliton, A. T. Lambertino, J. Liu, C. Xu, N. M. Munoz, and X. Zhu (2003)
J. Immunol. 171, 4399-4405
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Differential Activation of Formyl Peptide Receptor Signaling by Peptide Ligands.
Y.-S. Bae, J. Y. Song, Y. Kim, R. He, R. D. Ye, J.-Y. Kwak, P.-G. Suh, and S. H. Ryu (2003)
Mol. Pharmacol. 64, 841-847
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