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Science 287 (5455): 1046-1049

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

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}

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I. Boulven, S. Levasseur, S. Marois, G. Pare, E. Rollet-Labelle, and P. H. Naccache (2006)
J. Immunol. 176, 7621-7627
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Phosphatidylinositol 3-Kinase {gamma} Signaling through Protein Kinase C{zeta} Induces NADPH Oxidase-mediated Oxidant Generation and NF-{kappa}B Activation in Endothelial Cells.
R. S. Frey, X. Gao, K. Javaid, S. S. Siddiqui, A. Rahman, and A. B. Malik (2006)
J. Biol. Chem. 281, 16128-16138
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Evidence that phospholipase C-dependent, calcium-independent mechanisms are required for directional migration of T lymphocytes in response to the CCR4 ligands CCL17 and CCL22.
D. G. Cronshaw, A. Kouroumalis, R. Parry, A. Webb, Z. Brown, and S. G. Ward (2006)
J. Leukoc. Biol. 79, 1369-1380
   Abstract »    Full Text »    PDF »
Differential targeting of Gbetagamma-subunit signaling with small molecules..
T. M. Bonacci, J. L. Mathews, C. Yuan, D. M. Lehmann, S. Malik, D. Wu, J. L. Font, J. M. Bidlack, and A. V. Smrcka (2006)
Science 312, 443-446
   Abstract »    Full Text »    PDF »
Characterization of p87PIKAP, a Novel Regulatory Subunit of Phosphoinositide 3-Kinase {gamma} That Is Highly Expressed in Heart and Interacts with PDE3B.
P. Voigt, M. B. Dorner, and M. Schaefer (2006)
J. Biol. Chem. 281, 9977-9986
   Abstract »    Full Text »    PDF »
Knock-outs and inhibitors: one and the same?.
Z. A. Knight and K. M. Shokat (2006)
Blood 107, 420-421
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Key role of the p110{delta} isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110{delta} function in B cells.
A. Bilancio, K. Okkenhaug, M. Camps, J. L. Emery, T. Ruckle, C. Rommel, and B. Vanhaesebroeck (2006)
Blood 107, 642-650
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{beta}2-chimaerin provides a diacylglycerol-dependent mechanism for regulation of adhesion and chemotaxis of T cells.
M. Siliceo, D. Garcia-Bernal, S. Carrasco, E. Diaz-Flores, F. C. Leskow, J. Teixido, M. G. Kazanietz, and I. Merida (2006)
J. Cell Sci. 119, 141-152
   Abstract »    Full Text »    PDF »
HIV-1 burden influences host response to co-infection with Neisseria gonorrhoeae in vitro.
M. Montano, M. Rarick, P. Sebastiani, P. Brinkmann, J. Skefos, and R. Ericksen (2006)
Int. Immunol. 18, 125-137
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Phosphoinositide 3-Kinase Activity Controls the Chemoattractant-mediated Activation and Adaptation of Adenylyl Cyclase.
F. I. Comer and C. A. Parent (2006)
Mol. Biol. Cell 17, 357-366
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Targeted Deletion of Integrin-Linked Kinase Reveals a Role in T-Cell Chemotaxis and Survival.
E. Liu, S. Sinha, C. Williams, M. Cyrille, E. Heller, S. B. Snapper, K. Georgopoulos, R. St-Arnaud, T. Force, S. Dedhar, et al. (2005)
Mol. Cell. Biol. 25, 11145-11155
   Abstract »    Full Text »    PDF »
Plasma Membrane Organization Is Essential for Balancing Competing Pseudopod- and Uropod-promoting Signals during Neutrophil Polarization and Migration.
S. Bodin and M. D. Welch (2005)
Mol. Biol. Cell 16, 5773-5783
   Abstract »    Full Text »    PDF »
Mammalian G Proteins and Their Cell Type Specific Functions.
N. Wettschureck and S. Offermanns (2005)
Physiol Rev 85, 1159-1204
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"Host Tissue Damage" Signal ATP Promotes Non-directional Migration and Negatively Regulates Toll-like Receptor Signaling in Human Monocytes.
A. Kaufmann, B. Musset, S. H. Limberg, V. Renigunta, R. Sus, A. H. Dalpke, K. M. Heeg, B. Robaye, and P. J. Hanley (2005)
J. Biol. Chem. 280, 32459-32467
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