Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 287 (5455): 1049-1053

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

Central Role for G Protein-Coupled Phosphoinositide 3-Kinase gamma  in Inflammation

Emilio Hirsch, 1* Vladimir L. Katanaev, 2 Cecilia Garlanda, 3 Ornella Azzolino, 1 Luciano Pirola, 2 Lorenzo Silengo, 1 Silvano Sozzani, 3 Alberto Mantovani, 34 Fiorella Altruda, 1dagger Matthias P. Wymann 2*dagger

Phosphoinositide 3-kinase (PI3K) activity is crucial for leukocyte function, but the roles of the four receptor-activated isoforms are unclear. Mice lacking heterotrimeric guanine nucleotide-binding protein (G protein)-coupled PI3Kgamma were viable and had fully differentiated neutrophils and macrophages. Chemoattractant-stimulated PI3Kgamma -/- neutrophils did not produce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kinase B, and displayed impaired respiratory burst and motility. Peritoneal PI3Kgamma -null macrophages showed a reduced migration toward a wide range of chemotactic stimuli and a severely defective accumulation in a septic peritonitis model. These results demonstrate that PI3Kgamma is a crucial signaling molecule required for macrophage accumulation in inflammation.

1 Department of Genetics, Biology and Biochemistry, University of Torino, Turin, Italy.
2 Institute of Biochemistry, University of Fribourg, CH-1700 Fribourg, Switzerland.
3 Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
4 Section of General Pathology, University of Brescia, Brescia, Italy.
*   To whom correspondence should be addressed. E-mail: hirsch{at}molinette.unito.it and matthiaspaul.wymann{at}unifr.ch

dagger    These authors contributed equally to this work.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Elastin-derived peptides potentiate atherosclerosis through the immune Neu1-PI3K{gamma} pathway.
S. Gayral, R. Garnotel, A. Castaing-Berthou, S. Blaise, A. Fougerat, E. Berge, A. Montheil, N. Malet, M. P. Wymann, P. Maurice, et al. (2014)
Cardiovasc Res 102, 118-127
   Abstract »    Full Text »    PDF »
Novel Phosphoinositide 3-Kinase {delta},{gamma} Inhibitor: Potent Anti-Inflammatory Effects and Joint Protection in Models of Rheumatoid Arthritis.
D. L. Boyle, H.-R. Kim, K. Topolewski, B. Bartok, and G. S. Firestein (2014)
J. Pharmacol. Exp. Ther. 348, 271-280
   Abstract »    Full Text »    PDF »
DAPK2 positively regulates motility of neutrophils and eosinophils in response to intermediary chemoattractants.
B. Geering, C. Stoeckle, S. Rozman, K. Oberson, C. Benarafa, and H.-U. Simon (2014)
J. Leukoc. Biol. 95, 293-303
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence.
E. Sapey, H. Greenwood, G. Walton, E. Mann, A. Love, N. Aaronson, R. H. Insall, R. A. Stockley, and J. M. Lord (2014)
Blood 123, 239-248
   Abstract »    Full Text »    PDF »
Molecular determinants of PI3K{gamma}-mediated activation downstream of G-protein-coupled receptors (GPCRs).
O. Vadas, H. A. Dbouk, A. Shymanets, O. Perisic, J. E. Burke, W. F. Abi Saab, B. D. Khalil, C. Harteneck, A. R. Bresnick, B. Nurnberg, et al. (2013)
PNAS 110, 18862-18867
   Abstract »    Full Text »    PDF »
Cross Talk between the Akt and p38{alpha} Pathways in Macrophages Downstream of Toll-Like Receptor Signaling.
V. A. McGuire, A. Gray, C. E. Monk, S. G. Santos, K. Lee, A. Aubareda, J. Crowe, N. Ronkina, J. Schwermann, I. H. Batty, et al. (2013)
Mol. Cell. Biol. 33, 4152-4165
   Abstract »    Full Text »    PDF »
Mammalian target of rapamycin and Rictor control neutrophil chemotaxis by regulating Rac/Cdc42 activity and the actin cytoskeleton.
Y. He, D. Li, S. L. Cook, M.-S. Yoon, A. Kapoor, C. V. Rao, P. J. A. Kenis, J. Chen, and F. Wang (2013)
Mol. Biol. Cell 24, 3369-3380
   Abstract »    Full Text »    PDF »
Molecular players in neutrophil chemotaxis--focus on PI3K and small GTPases.
L. Gambardella and S. Vermeren (2013)
J. Leukoc. Biol. 94, 603-612
   Abstract »    Full Text »    PDF »
Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation.
T. Balla (2013)
Physiol Rev 93, 1019-1137
   Abstract »    Full Text »    PDF »
Cyclooxygenase-2 Deficiency in Macrophages Leads to Defective p110{gamma} PI3K Signaling and Impairs Cell Adhesion and Migration.
M. D. Diaz-Munoz, I. C. Osma-Garcia, M. A. Iniguez, and M. Fresno (2013)
J. Immunol. 191, 395-406
   Abstract »    Full Text »    PDF »
Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration.
W. K. A. Karunarathne, L. Giri, A. K. Patel, K. V. Venkatesh, and N. Gautam (2013)
PNAS 110, E1575-E1583
   Abstract »    Full Text »    PDF »
Class I Phosphoinositide-3-Kinases and Src Kinases Play a Nonredundant Role in Regulation of Adhesion-Independent and -Dependent Neutrophil Reactive Oxygen Species Generation.
L. Fumagalli, C. C. Campa, G. Germena, C. A. Lowell, E. Hirsch, and G. Berton (2013)
J. Immunol. 190, 3648-3660
   Abstract »    Full Text »    PDF »
Molecular mechanisms of spontaneous and directed mast cell motility.
J. Lee, S. L. Veatch, B. Baird, and D. Holowka (2012)
J. Leukoc. Biol. 92, 1029-1041
   Abstract »    Full Text »    PDF »
Blockade of Phosphatidylinositol 3-Kinase (PI3K){delta} or PI3K{gamma} Reduces IL-17 and Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis.
A. Roller, A. Perino, P. Dapavo, E. Soro, K. Okkenhaug, E. Hirsch, and H. Ji (2012)
J. Immunol. 189, 4612-4620
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-Kinase {gamma} Protects Against Catecholamine-Induced Ventricular Arrhythmia Through Protein Kinase A-Mediated Regulation of Distinct Phosphodiesterases.
A. Ghigo, A. Perino, H. Mehel, A. Zahradnikova Jr, F. Morello, J. Leroy, V. O. Nikolaev, F. Damilano, J. Cimino, E. De Luca, et al. (2012)
Circulation 126, 2073-2083
   Abstract »    Full Text »    PDF »
Inhibition of PI3K Signaling Spurs New Therapeutic Opportunities in Inflammatory/Autoimmune Diseases and Hematological Malignancies.
J. G. Foster, M. D. Blunt, E. Carter, and S. G. Ward (2012)
Pharmacol. Rev. 64, 1027-1054
   Abstract »    Full Text »    PDF »
GPCR activation of Ras and PI3K{gamma} in neutrophils depends on PLC{beta}2/{beta}3 and the RasGEF RasGRP4.
S. Suire, C. Lecureuil, K. E. Anderson, G. Damoulakis, I. Niewczas, K. Davidson, H. Guillou, D. Pan, J. Clark, P. T. Hawkins, et al. (2012)
EMBO J. 31, 3118-3129
   Abstract »    Full Text »    PDF »
The p110{alpha} and p110{beta} isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis.
T. Utermark, T. Rao, H. Cheng, Q. Wang, S. H. Lee, Z. C. Wang, J. D. Iglehart, T. M. Roberts, W. J. Muller, and J. J. Zhao (2012)
Genes & Dev. 26, 1573-1586
   Abstract »    Full Text »    PDF »
GBF1 bears a novel phosphatidylinositol-phosphate binding module, BP3K, to link PI3K{gamma} activity with Arf1 activation involved in GPCR-mediated neutrophil chemotaxis and superoxide production.
Y. Mazaki, Y. Nishimura, and H. Sabe (2012)
Mol. Biol. Cell 23, 2457-2467
   Abstract »    Full Text »    PDF »
TGF-{beta} and Smad3 modulate PI3K/Akt signaling pathway in vascular smooth muscle cells.
P. A. Suwanabol, S. M. Seedial, F. Zhang, X. Shi, Y. Si, B. Liu, and K. C. Kent (2012)
Am J Physiol Heart Circ Physiol 302, H2211-H2219
   Abstract »    Full Text »    PDF »
Phosphoinositide lipid phosphatase SHIP1 and PTEN coordinate to regulate cell migration and adhesion.
S. Mondal, K. K. Subramanian, J. Sakai, B. Bajrami, and H. R. Luo (2012)
Mol. Biol. Cell 23, 1219-1230
   Abstract »    Full Text »    PDF »
Murine bone marrow-derived macrophages differentiated with GM-CSF become foam cells by PI3K{gamma}-dependent fluid-phase pinocytosis of native LDL.
J. J. Anzinger, J. Chang, Q. Xu, M. K. Barthwal, T. Bohnacker, M. P. Wymann, and H. S. Kruth (2012)
J. Lipid Res. 53, 34-42
   Abstract »    Full Text »    PDF »
The WD40 Repeat Protein WDR26 Binds G{beta}{gamma} and Promotes G{beta}{gamma}-dependent Signal Transduction and Leukocyte Migration.
Z. Sun, X. Tang, F. Lin, and S. Chen (2011)
J. Biol. Chem. 286, 43902-43912
   Abstract »    Full Text »    PDF »
PTEN Negatively Regulates Engulfment of Apoptotic Cells by Modulating Activation of Rac GTPase.
S. Mondal, S. Ghosh-Roy, F. Loison, Y. Li, Y. Jia, C. Harris, D. A. Williams, and H. R. Luo (2011)
J. Immunol. 187, 5783-5794
   Abstract »    Full Text »    PDF »
Interaction of Ras with P110{gamma} Is Required for Thymic {beta}-Selection in the Mouse.
M. L. Janas and M. Turner (2011)
J. Immunol. 187, 4667-4675
   Abstract »    Full Text »    PDF »
PI3K{gamma} within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance.
B. Becattini, R. Marone, F. Zani, D. Arsenijevic, J. Seydoux, J.-P. Montani, A. G. Dulloo, B. Thorens, F. Preitner, M. P. Wymann, et al. (2011)
PNAS 108, E854-E863
   Abstract »    Full Text »    PDF »
Enhanced Phosphoinositide 3-Kinase {delta} Activity Is a Frequent Event in Systemic Lupus Erythematosus That Confers Resistance to Activation-Induced T Cell Death.
A. Suarez-Fueyo, D. F. Barber, J. Martinez-Ara, A. C. Zea-Mendoza, and A. C. Carrera (2011)
J. Immunol. 187, 2376-2385
   Abstract »    Full Text »    PDF »
The RacGAP ArhGAP15 is a master negative regulator of neutrophil functions.
C. Costa, G. Germena, E. L. Martin-Conte, I. Molineris, E. Bosco, S. Marengo, O. Azzolino, F. Altruda, V. M. Ranieri, and E. Hirsch (2011)
Blood 118, 1099-1108
   Abstract »    Full Text »    PDF »
Phosphatidylinositol-3-Kinase Gamma Plays a Central Role in Blood-Brain Barrier Dysfunction in Acute Experimental Stroke.
R. Jin, Z. Song, S. Yu, A. Piazza, A. Nanda, J. M. Penninger, D. N. Granger, and G. Li (2011)
Stroke 42, 2033-2044
   Abstract »    Full Text »    PDF »
PI3K{gamma} controls leukocyte recruitment, tissue injury, and lethality in a model of graft-versus-host disease in mice.
M. G. M. Castor, B. M. Rezende, P. T. T. Bernardes, A. T. Vieira, E. L. M. Vieira, R. M. E. Arantes, D. G. Souza, T. A. Silva, M. M. Teixeira, and V. Pinho (2011)
J. Leukoc. Biol. 89, 955-964
   Abstract »    Full Text »    PDF »
PI3K and Chemotaxis: A Priming Issue?.
P. V. Afonso and C. A. Parent (2011)
Science Signaling 4, pe22
   Abstract »    Full Text »    PDF »
PI3K{beta} Plays a Critical Role in Neutrophil Activation by Immune Complexes.
S. Kulkarni, C. Sitaru, Z. Jakus, K. E. Anderson, G. Damoulakis, K. Davidson, M. Hirose, J. Juss, D. Oxley, T. A. M. Chessa, et al. (2011)
Science Signaling 4, ra23
   Abstract »    Full Text »    PDF »
Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance.
N. Kobayashi, K. Ueki, Y. Okazaki, A. Iwane, N. Kubota, M. Ohsugi, M. Awazawa, M. Kobayashi, T. Sasako, K. Kaneko, et al. (2011)
PNAS 108, 5753-5758
   Abstract »    Full Text »    PDF »
Class IA Phosphoinositide 3-Kinase {beta} and {delta} Regulate Neutrophil Oxidase Activation in Response to Aspergillus fumigatus Hyphae.
K. B. Boyle, D. Gyori, A. Sindrilaru, K. Scharffetter-Kochanek, P. R. Taylor, A. Mocsai, L. R. Stephens, and P. T. Hawkins (2011)
J. Immunol. 186, 2978-2989
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-kinase {gamma} plays a critical role in bleomycin-induced pulmonary inflammation and fibrosis in mice.
R. C. Russo, C. C. Garcia, L. S. Barcelos, M. A. Rachid, R. Guabiraba, E. Roffe, A. L. S. Souza, L. P. Sousa, M. Mirolo, A. Doni, et al. (2011)
J. Leukoc. Biol. 89, 269-282
   Abstract »    Full Text »    PDF »
Distinct Effects of Leukocyte and Cardiac Phosphoinositide 3-Kinase {gamma} Activity in Pressure Overload-Induced Cardiac Failure.
F. Damilano, I. Franco, C. Perrino, K. Schaefer, O. Azzolino, D. Carnevale, G. Cifelli, P. Carullo, R. Ragona, A. Ghigo, et al. (2011)
Circulation 123, 391-399
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-Kinase-Dependent Antagonism in Mammalian Olfactory Receptor Neurons.
K. Ukhanov, D. Brunert, E. A. Corey, and B. W. Ache (2011)
J. Neurosci. 31, 273-280
   Abstract »    Full Text »    PDF »
Rational Design of a Selective Covalent Modifier of G Protein {beta}{gamma} Subunits.
A. L. Dessal, R. Prades, E. Giralt, and A. V. Smrcka (2011)
Mol. Pharmacol. 79, 24-33
   Abstract »    Full Text »    PDF »
Understanding the Structure and Function of the Immunological Synapse.
M. L. Dustin, A. K. Chakraborty, and A. S. Shaw (2010)
Cold Spring Harb Perspect Biol 2, a002311
   Abstract »    Full Text »    PDF »
Autocrine Purinergic Receptor Signaling Is Essential for Macrophage Chemotaxis.
M. Kronlage, J. Song, L. Sorokin, K. Isfort, T. Schwerdtle, J. Leipziger, B. Robaye, P. B. Conley, H.-C. Kim, S. Sargin, et al. (2010)
Science Signaling 3, ra55
   Abstract »    Full Text »    PDF »
Important roles of PI3K{gamma} in osteoclastogenesis and bone homeostasis.
H. Kang, W. Chang, M. Hurley, A. Vignery, and D. Wu (2010)
PNAS 107, 12901-12906
   Abstract »    Full Text »    PDF »
Myeloid PTEN Promotes Inflammation but Impairs Bactericidal Activities during Murine Pneumococcal Pneumonia.
G. Schabbauer, U. Matt, P. Gunzl, J. Warszawska, T. Furtner, E. Hainzl, I. Elbau, I. Mesteri, B. Doninger, B. R. Binder, et al. (2010)
J. Immunol. 185, 468-476
   Abstract »    Full Text »    PDF »
The catalytic PI3K isoforms p110{gamma} and p110{delta} contribute to B cell development and maintenance, transformation, and proliferation.
S. Beer-Hammer, E. Zebedin, M. von Holleben, J. Alferink, B. Reis, P. Dresing, D. Degrandi, S. Scheu, E. Hirsch, V. Sexl, et al. (2010)
J. Leukoc. Biol. 87, 1083-1095
   Abstract »    Full Text »    PDF »
Akt isoforms differentially regulate neutrophil functions.
J. Chen, H. Tang, N. Hay, J. Xu, and R. D. Ye (2010)
Blood 115, 4237-4246
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-kinase {gamma} required for lipopolysaccharide-induced transepithelial neutrophil trafficking in the lung.
J. Reutershan, M. S. Saprito, D. Wu, T. Ruckle, and K. Ley (2010)
Eur. Respir. J. 35, 1137-1147
   Abstract »    Full Text »    PDF »
PI3K{gamma}-Dependent Signaling in Mouse Olfactory Receptor Neurons.
D. Brunert, K. Klasen, E. A. Corey, and B. W. Ache (2010)
Chem Senses 35, 301-308
   Abstract »    Full Text »    PDF »
Molecular regulators of leucocyte chemotaxis during inflammation.
C. H. Y. Wong, B. Heit, and P. Kubes (2010)
Cardiovasc Res 86, 183-191
   Abstract »    Full Text »    PDF »
Tyrosine kinase Btk regulates E-selectin-mediated integrin activation and neutrophil recruitment by controlling phospholipase C (PLC) {gamma}2 and PI3K{gamma} pathways.
H. Mueller, A. Stadtmann, H. Van Aken, E. Hirsch, D. Wang, K. Ley, and A. Zarbock (2010)
Blood 115, 3118-3127
   Abstract »    Full Text »    PDF »
Involvement of Phosphoinositide 3-Kinase {gamma} in Angiogenesis and Healing of Experimental Myocardial Infarction in Mice.
M. Siragusa, R. Katare, M. Meloni, F. Damilano, E. Hirsch, C. Emanueli, and P. Madeddu (2010)
Circ. Res. 106, 757-768
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 3-kinase isoforms as targets in respiratory disease.
J. A. Marwick, Kian Fan Chung, and I. M. Adcock (2010)
Therapeutic Advances in Respiratory Disease 4, 19-34
   Abstract »    PDF »
Inhibitory Odorant Signaling in Mammalian Olfactory Receptor Neurons.
K. Ukhanov, E. A. Corey, D. Brunert, K. Klasen, and B. W. Ache (2010)
J Neurophysiol 103, 1114-1122
   Abstract »    Full Text »    PDF »
NMR analysis of G-protein {beta}{gamma} subunit complexes reveals a dynamic G{alpha}-G{beta}{gamma} subunit interface and multiple protein recognition modes.
A. V. Smrcka, N. Kichik, T. Tarrago, M. Burroughs, M.-S. Park, N. K. Itoga, H. A. Stern, B. M. Willardson, and E. Giralt (2010)
PNAS 107, 639-644
   Abstract »    Full Text »    PDF »
Inhibition of Phosphoinositide 3-Kinase Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mice.
X.-d. Peng, X.-h. Wu, L.-j. Chen, Z.-l. Wang, X.-h. Hu, L.-f. Song, C.-m. He, Y.-f. Luo, Z.-z. Chen, K. Jin, et al. (2010)
J. Pharmacol. Exp. Ther. 332, 46-56
   Abstract »    Full Text »    PDF »
Ras is an indispensable coregulator of the class IB phosphoinositide 3-kinase p87/p110{gamma}.
B. Kurig, A. Shymanets, T. Bohnacker, Prajwal, C. Brock, M. R. Ahmadian, M. Schaefer, A. Gohla, C. Harteneck, M. P. Wymann, et al. (2009)
PNAS 106, 20312-20317
   Abstract »    Full Text »    PDF »
PI3K{gamma} regulates cartilage damage in chronic inflammatory arthritis.
S. Hayer, N. Pundt, M. A. Peters, C. Wunrau, I. Kuhnel, K. Neugebauer, S. Strietholt, J. Zwerina, A. Korb, J. Penninger, et al. (2009)
FASEB J 23, 4288-4298
   Abstract »    Full Text »    PDF »
Erythrocyte scaffolding protein p55/MPP1 functions as an essential regulator of neutrophil polarity.
B. J. Quinn, E. J. Welch, A. C. Kim, M. A. Lokuta, A. Huttenlocher, A. A. Khan, S. M. Kuchay, and A. H. Chishti (2009)
PNAS 106, 19842-19847
   Abstract »    Full Text »    PDF »
The Signaling Mechanisms Underlying Cell Polarity and Chemotaxis.
F. Wang (2009)
Cold Spring Harb Perspect Biol 1, a002980
   Abstract »    Full Text »    PDF »
The functional significance behind expressing two IL-8 receptor types on PMN.
R. Stillie, S. M. Farooq, J. R. Gordon, and A. W. Stadnyk (2009)
J. Leukoc. Biol. 86, 529-543
   Abstract »    Full Text »    PDF »
Akt1 is critical for acute inflammation and histamine-mediated vascular leakage.
A. Di Lorenzo, C. Fernandez-Hernando, G. Cirino, and W. C. Sessa (2009)
PNAS 106, 14552-14557
   Abstract »    Full Text »    PDF »
Regulation of the Src Homology 2 Domain-containing Inositol 5'-Phosphatase (SHIP1) by the Cyclic AMP-dependent Protein Kinase.
J. Zhang, S. F. Walk, K. S. Ravichandran, and J. C. Garrison (2009)
J. Biol. Chem. 284, 20070-20078
   Abstract »    Full Text »    PDF »
Finding Partners for PI3K{gamma}: When 84 Is Better Than 101.
T. Balla (2009)
Science Signaling 2, pe35
   Abstract »    Full Text »    PDF »
PI3K{gamma} Adaptor Subunits Define Coupling to Degranulation and Cell Motility by Distinct PtdIns(3,4,5)P3 Pools in Mast Cells.
T. Bohnacker, R. Marone, E. Collmann, R. Calvez, E. Hirsch, and M. P. Wymann (2009)
Science Signaling 2, ra27
   Abstract »    Full Text »    PDF »
Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans.
K. L. Weaver, P. Ivester, M. Seeds, L. D. Case, J. P. Arm, and F. H. Chilton (2009)
J. Biol. Chem. 284, 15400-15407
   Abstract »    Full Text »    PDF »
Myeloid-Specific Deletion of Tumor Suppressor PTEN Augments Neutrophil Transendothelial Migration during Inflammation.
B. Sarraj, S. Massberg, Y. Li, A. Kasorn, K. Subramanian, F. Loison, L. E. Silberstein, U. von Andrian, and H. R. Luo (2009)
J. Immunol. 182, 7190-7200
   Abstract »    Full Text »    PDF »
International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the Formyl Peptide Receptor (FPR) Family.
R. D. Ye, F. Boulay, J. M. Wang, C. Dahlgren, C. Gerard, M. Parmentier, C. N. Serhan, and P. M. Murphy (2009)
Pharmacol. Rev. 61, 119-161
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-kinase signalling in the vascular system.
F. Morello, A. Perino, and E. Hirsch (2009)
Cardiovasc Res 82, 261-271
   Abstract »    Full Text »    PDF »
Leptin enhances cell migration in human chondrosarcoma cells through OBRl leptin receptor.
S.-N. Yang, H.-T. Chen, H.-K. Tsou, C.-Y. Huang, W.-H. Yang, C.-M. Su, Y.-C. Fong, W.-P. Tseng, and C.-H. Tang (2009)
Carcinogenesis 30, 566-574
   Abstract »    Full Text »    PDF »
Aerosolized Phosphoinositide 3-Kinase {gamma}/{delta} Inhibitor TG100-115 [3-[2,4-Diamino-6-(3-hydroxyphenyl)pteridin-7-yl]phenol] as a Therapeutic Candidate for Asthma and Chronic Obstructive Pulmonary Disease.
J. Doukas, L. Eide, K. Stebbins, A. Racanelli-Layton, L. Dellamary, M. Martin, E. Dneprovskaia, G. Noronha, R. Soll, W. Wrasidlo, et al. (2009)
J. Pharmacol. Exp. Ther. 328, 758-765
   Abstract »    Full Text »    PDF »
Negative Regulation of Class IA Phosphoinositide 3-kinase by Protein Kinase C{delta} Limits Fc{gamma} Receptor-Mediated Phagocytosis in Macrophages.
K. Hazeki, K. Inoue, K. Nigorikawa, and O. Hazeki (2009)
J. Biochem. 145, 87-94
   Abstract »    Full Text »    PDF »
CD18-dependent activation of the neutrophil NADPH oxidase during phagocytosis of Escherichia coli or Staphylococcus aureus is regulated by class III but not class I or II PI3Ks.
K. E. Anderson, K. B. Boyle, K. Davidson, T. A. M. Chessa, S. Kulkarni, G. E. Jarvis, A. Sindrilaru, K. Scharffetter-Kochanek, O. Rausch, L. R. Stephens, et al. (2008)
Blood 112, 5202-5211
   Abstract »    Full Text »    PDF »
The PI3K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications.
T Weichhart and M D Saemann (2008)
Ann Rheum Dis 67, iii70-iii74
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-Kinases {gamma} and {delta}, Linkers of Coordinate C5a Receptor-Fc{gamma} Receptor Activation and Immune Complex-induced Inflammation.
S. Konrad, S. R. Ali, K. Wiege, S. N. Syed, L. Engling, R. P. Piekorz, E. Hirsch, B. Nurnberg, R. E. Schmidt, and J. E. Gessner (2008)
J. Biol. Chem. 283, 33296-33303
   Abstract »    Full Text »    PDF »
Temporally controlled overexpression of cardiac-specific PI3K{alpha} induces enhanced myocardial contractility--a new transgenic model.
N. Yano, A. Tseng, T. C. Zhao, J. Robbins, J. F. Padbury, and Y.-T. Tseng (2008)
Am J Physiol Heart Circ Physiol 295, H1690-H1694
   Abstract »    Full Text »    PDF »
Overlapping and distinct roles for PI3K{beta} and {gamma} isoforms in S1P-induced migration of human and mouse endothelial cells.
R. Heller, Q. Chang, G. Ehrlich, S. N. Hsieh, S. M. Schoenwaelder, P. J. Kuhlencordt, K. T. Preissner, E. Hirsch, and R. Wetzker (2008)
Cardiovasc Res 80, 96-105
   Abstract »    Full Text »    PDF »
Parallel Phosphatidylinositol 3-Kinase (PI3K)-dependent and Src-dependent Pathways Lead to CXCL8-mediated Rac2 Activation and Chemotaxis.
J. Sai, D. Raman, Y. Liu, J. Wikswo, and A. Richmond (2008)
J. Biol. Chem. 283, 26538-26547
   Abstract »    Full Text »    PDF »
The p110{gamma} isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites.
M. S. Thomas, J. S. Mitchell, C. C. DeNucci, A. L. Martin, and Y. Shimizu (2008)
J. Leukoc. Biol. 84, 814-823
   Abstract »    Full Text »    PDF »
Neurokinin A engages neurokinin-1 receptor to induce NF-{kappa}B-dependent gene expression in murine macrophages: implications of ERK1/2 and PI 3-kinase/Akt pathways.
J. Sun, R. D. Ramnath, R. Tamizhselvi, and M. Bhatia (2008)
Am J Physiol Cell Physiol 295, C679-C691
   Abstract »    Full Text »    PDF »
The Inositol Phosphatase SHIP Controls Salmonella enterica Serovar Typhimurium Infection In Vivo.
J. L. Bishop, L. M. Sly, G. Krystal, and B. B. Finlay (2008)
Infect. Immun. 76, 2913-2922
   Abstract »    Full Text »    PDF »
Pain and the immune system.
H. L. Rittner, A. Brack, and C. Stein (2008)
Br. J. Anaesth. 101, 40-44
   Abstract »    Full Text »    PDF »
The p110{beta} isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110{gamma}.
J. Guillermet-Guibert, K. Bjorklof, A. Salpekar, C. Gonella, F. Ramadani, A. Bilancio, S. Meek, A. J. H. Smith, K. Okkenhaug, and B. Vanhaesebroeck (2008)
PNAS 105, 8292-8297
   Abstract »    Full Text »    PDF »
Signaling Mechanism of HIV-1 gp120 and Virion-Induced IL-1{beta} Release in Primary Human Macrophages.
R. Cheung, V. Ravyn, L. Wang, A. Ptasznik, and R. G. Collman (2008)
J. Immunol. 180, 6675-6684
   Abstract »    Full Text »    PDF »
Phosphatidylinositol-3-Kinase-{gamma} Is Integral to Homing Functions of Progenitor Cells.
E. Chavakis, G. Carmona, C. Urbich, S. Gottig, R. Henschler, J. M. Penninger, A. M. Zeiher, T. Chavakis, and S. Dimmeler (2008)
Circ. Res. 102, 942-949
   Abstract »    Full Text »    PDF »
Genetic and Pharmacological Targeting of Phosphoinositide 3-Kinase-{gamma} Reduces Atherosclerosis and Favors Plaque Stability by Modulating Inflammatory Processes.
A. Fougerat, S. Gayral, P. Gourdy, A. Schambourg, T. Ruckle, M. K. Schwarz, C. Rommel, E. Hirsch, J.-F. Arnal, J.-P. Salles, et al. (2008)
Circulation 117, 1310-1317
   Abstract »    Full Text »    PDF »
The regulation of cell motility and chemotaxis by phospholipid signaling.
V. Kolsch, P. G. Charest, and R. A. Firtel (2008)
J. Cell Sci. 121, 551-559
   Abstract »    Full Text »    PDF »
Four key signaling pathways mediating chemotaxis in Dictyostelium discoideum.
D. M. Veltman, I. Keizer-Gunnik, and P. J.M. Van Haastert (2008)
J. Cell Biol. 180, 747-753
   Abstract »    Full Text »    PDF »
Critical Roles of the p110{beta} Subtype of Phosphoinositide 3-Kinase in Lipopolysaccharide-Induced Akt Activation and Negative Regulation of Nitrite Production in RAW 264.7 Cells.
K. Tsukamoto, K. Hazeki, M. Hoshi, K. Nigorikawa, N. Inoue, T. Sasaki, and O. Hazeki (2008)
J. Immunol. 180, 2054-2061
   Abstract »    Full Text »    PDF »
Selective Regulation of CD8 Effector T Cell Migration by the p110{gamma} Isoform of Phosphatidylinositol 3-Kinase.
A. L. Martin, M. D. Schwartz, S. C. Jameson, and Y. Shimizu (2008)
J. Immunol. 180, 2081-2088
   Abstract »    Full Text »    PDF »
Isoform-Specific Functions of Phosphoinositide 3-Kinases: p110{delta} but Not p110{gamma} Promotes Optimal Allergic Responses In Vivo.
K. Ali, M. Camps, W. P. Pearce, H. Ji, T. Ruckle, N. Kuehn, C. Pasquali, C. Chabert, C. Rommel, and B. Vanhaesebroeck (2008)
J. Immunol. 180, 2538-2544
   Abstract »    Full Text »    PDF »
The Molecular Basis of VEGFR-1 Signal Transduction Pathways in Primary Human Monocytes.
V. Tchaikovski, G. Fellbrich, and J. Waltenberger (2008)
Arterioscler Thromb Vasc Biol 28, 322-328
   Abstract »    Full Text »    PDF »
Small Molecule Disruption of G Protein {beta}{gamma} Subunit Signaling Inhibits Neutrophil Chemotaxis and Inflammation.
D. M. Lehmann, A. M. P. B. Seneviratne, and A. V. Smrcka (2008)
Mol. Pharmacol. 73, 410-418
   Abstract »    Full Text »    PDF »
CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer.
F. Garcon, D. T. Patton, J. L. Emery, E. Hirsch, R. Rottapel, T. Sasaki, and K. Okkenhaug (2008)
Blood 111, 1464-1471
   Abstract »    Full Text »    PDF »
PI3K accelerates, but is not required for, neutrophil chemotaxis to fMLP.
B. Heit, L. Liu, P. Colarusso, K. D. Puri, and P. Kubes (2008)
J. Cell Sci. 121, 205-214
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-Kinase {gamma} Gene Knockout Impairs Postischemic Neovascularization and Endothelial Progenitor Cell Functions.
P. Madeddu, N. Kraenkel, L. S. Barcelos, M. Siragusa, P. Campagnolo, A. Oikawa, A. Caporali, A. Herman, O. Azzolino, L. Barberis, et al. (2008)
Arterioscler Thromb Vasc Biol 28, 68-76
   Abstract »    Full Text »    PDF »
PDZRhoGEF and myosin II localize RhoA activity to the back of polarizing neutrophil-like cells.
K. Wong, A. Van Keymeulen, and H. R. Bourne (2007)
J. Cell Biol. 179, 1141-1148
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882