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): 1040-1046

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

Function of PI3Kgamma in Thymocyte Development, T Cell Activation, and Neutrophil Migration

Takehiko Sasaki, 12 Junko Irie-Sasaki, 12 Russell G. Jones, 2 Antonio J. Oliveira-dos-Santos, 1 William L. Stanford, 3 Brad Bolon, 4 Andrew Wakeham, 1 Annick Itie, 1 Dennis Bouchard, 1 Ivona Kozieradzki, 1 Nicholas Joza, 1 Tak W. Mak, 12 Pamela S. Ohashi, 2 Akira Suzuki, 12 Josef M. Penninger 12*

Phosphoinositide 3-kinases (PI3Ks) regulate fundamental cellular responses such as proliferation, apoptosis, cell motility, and adhesion. Viable gene-targeted mice lacking the p110 catalytic subunit of PI3Kgamma were generated. We show that PI3Kgamma controls thymocyte survival and activation of mature T cells but has no role in the development or function of B cells. PI3Kgamma -deficient neutrophils exhibited severe defects in migration and respiratory burst in response to heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPCR) agonists and chemotactic agents. PI3Kgamma links GPCR stimulation to the formation of phosphatidylinositol 3,4,5-triphosphate and the activation of protein kinase B, ribosomal protein S6 kinase, and extracellular signal-regulated kinases 1 and 2. Thus, PI3Kgamma regulates thymocyte development, T cell activation, neutrophil migration, and the oxidative burst.

1 Amgen Institute, 620 University Avenue, Toronto M5G 2C1, Ontario, Canada.
2 Ontario Cancer Institute and the Departments of Medical Biophysics and Immunology;
3 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Medical Genetics, University of Toronto, Toronto M5G 2C1, Ontario, Canada.
4 Department of Pathology, Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320-1789, USA.
*   To whom correspondence should be addressed. E-mail: jpenning{at}amgen.com

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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 PI3K-mediated Akt and ERK signals play a critical role in Fc{varepsilon}RI-induced degranulation in mast cells.
G. Takayama, M. Ohtani, A. Minowa, S. Matsuda, and S. Koyasu (2013)
Int. Immunol. 25, 215-220
   Abstract »    Full Text »    PDF »
Critical roles of type III phosphatidylinositol phosphate kinase in murine embryonic visceral endoderm and adult intestine.
S. Takasuga, Y. Horie, J. Sasaki, G.-H. Sun-Wada, N. Kawamura, R. Iizuka, K. Mizuno, S. Eguchi, S. Kofuji, H. Kimura, et al. (2013)
PNAS 110, 1726-1731
   Abstract »    Full Text »    PDF »
Essential Role of Class II Phosphatidylinositol-3-kinase-C2{alpha} in Sphingosine 1-Phosphate Receptor-1-mediated Signaling and Migration in Endothelial Cells.
K. Biswas, K. Yoshioka, K. Asanuma, Y. Okamoto, N. Takuwa, T. Sasaki, and Y. Takuwa (2013)
J. Biol. Chem. 288, 2325-2339
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-Kinase {gamma} Inhibits Cardiac GSK-3 Independently of Akt.
M. L. Mohan, B. K. Jha, M. K. Gupta, N. T. Vasudevan, E. E. Martelli, J. D. Mosinski, and S. V. Naga Prasad (2013)
Science Signaling 6, ra4
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 3-Kinase-{gamma} Signaling Promotes Campylobacter jejuni-Induced Colitis through Neutrophil Recruitment in Mice.
X. Sun, B. Liu, R. B. Sartor, and C. Jobin (2013)
J. Immunol. 190, 357-365
   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 »
Glucagon-like peptide 2 induces vasoactive intestinal polypeptide expression in enteric neurons via phophatidylinositol 3-kinase-{gamma} signaling.
E. de Heuvel, L. Wallace, K. A. Sharkey, and D. L. Sigalet (2012)
Am J Physiol Endocrinol Metab 303, E994-E1005
   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 »
The B-cell receptor signaling pathway as a therapeutic target in CLL.
J. A. Woyach, A. J. Johnson, and J. C. Byrd (2012)
Blood 120, 1175-1184
   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 »
The Novel Therapeutic Effect of Phosphoinositide 3-Kinase-{gamma} Inhibitor AS605240 in Autoimmune Diabetes.
J. Azzi, R. F. Moore, W. Elyaman, M. Mounayar, N. El Haddad, S. Yang, M. Jurewicz, A. Takakura, A. Petrelli, P. Fiorina, et al. (2012)
Diabetes 61, 1509-1518
   Abstract »    Full Text »    PDF »
Mammalian Target of Rapamycin Integrates Diverse Inputs To Guide the Outcome of Antigen Recognition in T Cells.
A. T. Waickman and J. D. Powell (2012)
J. Immunol. 188, 4721-4729
   Abstract »    Full Text »    PDF »
Actin polymerization stabilizes {alpha}4{beta}1 integrin anchors that mediate monocyte adhesion.
J. Rullo, H. Becker, S. J. Hyduk, J. C. Wong, G. Digby, P. D. Arora, A. P. Cano, J. Hartwig, C. A. McCulloch, and M. I. Cybulsky (2012)
J. Cell Biol. 197, 115-129
   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 »
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 »
Tripartite motif containing protein 27 negatively regulates CD4 T cells by ubiquitinating and inhibiting the class II PI3K-C2{beta}.
X. Cai, S. Srivastava, Y. Sun, Z. Li, H. Wu, L. Zuvela-Jelaska, J. Li, R. S. Salamon, J. M. Backer, and E. Y. Skolnik (2011)
PNAS 108, 20072-20077
   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 »
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 »
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 »
C5a controls TLR-induced IL-10 and IL-12 production independent of phosphoinositide 3-kinase.
N. Okazaki, K. Hazeki, T. Izumi, K. Nigorikawa, and O. Hazeki (2011)
J. Biochem. 149, 265-274
   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 »
Lipid Signaling in T-Cell Development and Function.
Y. H. Huang and K. Sauer (2010)
Cold Spring Harb Perspect Biol 2, a002428
   Abstract »    Full Text »    PDF »
Phosphoinositide-3 Kinase {gamma} Activity Contributes to Sepsis and Organ Damage by Altering Neutrophil Recruitment.
E. L. Martin, D. G. Souza, C. T. Fagundes, F. A. Amaral, B. Assenzio, V. Puntorieri, L. Del Sorbo, V. Fanelli, M. Bosco, L. Delsedime, et al. (2010)
182, 762-773
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 3-Kinase Signaling in Thymocytes: The Need for Stringent Control.
E. Fayard, G. Moncayo, B. A. Hemmings, and G. A. Hollander (2010)
Science Signaling 3, re5
   Abstract »    Full Text »    PDF »
STAT5 Is Critical To Maintain Effector CD8+ T Cell Responses.
P. Tripathi, S. Kurtulus, S. Wojciechowski, A. Sholl, K. Hoebe, S. C. Morris, F. D. Finkelman, H. L. Grimes, and D. A. Hildeman (2010)
J. Immunol. 185, 2116-2124
   Abstract »    Full Text »    PDF »
An Enigmatic Tail of CD28 Signaling.
J. S. Boomer and J. M. Green (2010)
Cold Spring Harb Perspect Biol 2, a002436
   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 »
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 »
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 »
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 »
The Alarmin Cytokine, High Mobility Group Box 1, Is Produced by Viable Cardiomyocytes and Mediates the Lipopolysaccharide-Induced Myocardial Dysfunction via a TLR4/Phosphatidylinositol 3-Kinase {gamma} Pathway.
H. Xu, Z. Su, J. Wu, M. Yang, J. M. Penninger, C. M. Martin, P. R. Kvietys, and T. Rui (2010)
J. Immunol. 184, 1492-1498
   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 »
PDK1 Regulates Chemotaxis in Human Neutrophils.
M. Yagi, A. Kantarci, T. Iwata, K. Omori, S. Ayilavarapu, K. Ito, H. Hasturk, and T. E. Van Dyke (2009)
Journal of Dental Research 88, 1119-1124
   Abstract »    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 Class II Phosphatidylinositol 3 kinase C2{beta} Is Required for the Activation of the K+ Channel KCa3.1 and CD4 T-Cells.
S. Srivastava, L. Di, O. Zhdanova, Z. Li, S. Vardhana, Q. Wan, Y. Yan, R. Varma, J. Backer, H. Wulff, et al. (2009)
Mol. Biol. Cell 20, 3783-3791
   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 »
CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway.
K. Gollmer, F. Asperti-Boursin, Y. Tanaka, K. Okkenhaug, B. Vanhaesebroeck, J. R. Peterson, Y. Fukui, E. Donnadieu, and J. V. Stein (2009)
Blood 114, 580-588
   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 »
CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells.
R. A. Vongsa, N. P. Zimmerman, and M. B. Dwinell (2009)
J. Biol. Chem. 284, 10034-10045
   Abstract »    Full Text »    PDF »
p85{beta} phosphoinositide 3-kinase regulates CD28 coreceptor function.
I. Alcazar, I. Cortes, A. Zaballos, C. Hernandez, D. A. Fruman, D. F. Barber, and A. C. Carrera (2009)
Blood 113, 3198-3208
   Abstract »    Full Text »    PDF »
Inhibition of PI3K{delta} Restores Glucocorticoid Function in Smoking-induced Airway Inflammation in Mice.
J. A. Marwick, G. Caramori, C. S. Stevenson, P. Casolari, E. Jazrawi, P. J. Barnes, K. Ito, I. M. Adcock, P. A. Kirkham, and A. Papi (2009)
179, 542-548
   Abstract »    Full Text »    PDF »
PI3K{gamma}-deficient mice have reduced levels of allergen-induced eosinophilic inflammation and airway remodeling.
D. H. Lim, J. Y. Cho, D. J. Song, S. Y. Lee, M. Miller, and D. H. Broide (2009)
Am J Physiol Lung Cell Mol Physiol 296, L210-L219
   Abstract »    Full Text »    PDF »
Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy.
N. T. Ihle and G. Powis (2009)
Mol. Cancer Ther. 8, 1-9
   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 »
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 »
Activity of the p110-{alpha} subunit of phosphatidylinositol-3-kinase is required for activation of epithelial sodium transport.
J. Wang, Z. A. Knight, D. Fiedler, O. Williams, K. M. Shokat, and D. Pearce (2008)
Am J Physiol Renal Physiol 295, F843-F850
   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 »
CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1.
T. T. Murooka, R. Rahbar, L. C. Platanias, and E. N. Fish (2008)
Blood 111, 4892-4901
   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 »
Enhancement of neutrophil function by the bronchial epithelium stimulated by epidermal growth factor.
M. Uddin, G. Seumois, L. C. Lau, P. Rytila, D. E. Davies, and R. Djukanovic (2008)
Eur. Respir. J. 31, 714-724
   Abstract »    Full Text »    PDF »
Phosphatidylinositol-3-Kinase-Atypical Protein Kinase C Signaling Is Required for Wnt Attraction and Anterior-Posterior Axon Guidance.
A. M. Wolf, A. I. Lyuksyutova, A. G. Fenstermaker, B. Shafer, C. G. Lo, and Y. Zou (2008)
J. Neurosci. 28, 3456-3467
   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 »
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 »
Phosphoinositide Lipid Phosphatases: Natural Regulators of Phosphoinositide 3-Kinase Signaling in T Lymphocytes.
S. J. Harris, R. V. Parry, J. Westwick, and S. G. Ward (2008)
J. Biol. Chem. 283, 2465-2469
   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 »
Leptin Induces Macrophage Lipid Body Formation by a Phosphatidylinositol 3-Kinase- and Mammalian Target of Rapamycin-dependent Mechanism.
C. M. Maya-Monteiro, P. E. Almeida, H. D'Avila, A. S. Martins, A. P. Rezende, H. Castro-Faria-Neto, and P. T. Bozza (2008)
J. Biol. Chem. 283, 2203-2210
   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 »
Protein kinase B (c-akt) regulates hematopoietic lineage choice decisions during myelopoiesis.
M. Buitenhuis, L. P. Verhagen, H. W. M. van Deutekom, A. Castor, S. Verploegen, L. Koenderman, S.-E. W. Jacobsen, and P. J. Coffer (2008)
Blood 111, 112-121
   Abstract »    Full Text »    PDF »
Altered Heart Rate and Sinoatrial Node Function in Mice Lacking the cAMP Regulator Phosphoinositide 3-Kinase-{gamma}.
R. A. Rose, M. G. Kabir, and P. H. Backx (2007)
Circ. Res. 101, 1274-1282
   Abstract »    Full Text »    PDF »
Tissue- and Stimulus-Dependent Role of Phosphatidylinositol 3-Kinase Isoforms for Neutrophil Recruitment Induced by Chemoattractants In Vivo.
V. Pinho, R. de Castro Russo, F. A. Amaral, L. P. de Sousa, M. M. Barsante, D. G. de Souza, J. C. Alves-Filho, D. C. Cara, J. S. Hayflick, C. Rommel, et al. (2007)
J. Immunol. 179, 7891-7898
   Abstract »    Full Text »    PDF »
Endothelial PI 3-kinase activity regulates lymphocyte diapedesis.
M. Nakhaei-Nejad, A. M. Hussain, Q.-X. Zhang, and A. G. Murray (2007)
Am J Physiol Heart Circ Physiol 293, H3608-H3616
   Abstract »    Full Text »    PDF »
Phosphoinositide 3 kinase {gamma} participates in T cell receptor induced T cell activation.
I. Alcazar, M. Marques, A. Kumar, E. Hirsch, M. Wymann, A. C. Carrera, and D. F. Barber (2007)
J. Exp. Med. 204, 2977-2987
   Abstract »    Full Text »    PDF »
Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes.
G. Shi, S. Partida-Sanchez, R. S. Misra, M. Tighe, M. T. Borchers, J. J. Lee, M. I. Simon, and F. E. Lund (2007)
J. Exp. Med. 204, 2705-2718
   Abstract »    Full Text »    PDF »
Inactivation of PI3K{gamma} and PI3K{delta} distorts T-cell development and causes multiple organ inflammation.
H. Ji, F. Rintelen, C. Waltzinger, D. Bertschy Meier, A. Bilancio, W. Pearce, E. Hirsch, M. P. Wymann, T. Ruckle, M. Camps, et al. (2007)
Blood 110, 2940-2947
   Abstract »    Full Text »    PDF »
PI3K Class IB Pathway.
S. Andrews, L. R. Stephens, and P. T. Hawkins (2007)
Sci. STKE 2007, cm2
   Abstract »    Full Text »    PDF »
Negative feedback regulation of Rac in leukocytes from mice expressing a constitutively active phosphatidylinositol 3-kinase {gamma}.
C. Costa, L. Barberis, C. Ambrogio, A. D. Manazza, E. Patrucco, O. Azzolino, P. O. Neilsen, E. Ciraolo, F. Altruda, G. D. Prestwich, et al. (2007)
PNAS 104, 14354-14359
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-Kinase {gamma} Inhibition Plays a Crucial Role in Early Steps of Inflammation by Blocking Neutrophil Recruitment.
C. Ferrandi, V. Ardissone, P. Ferro, T. Ruckle, P. Zaratin, E. Ammannati, E. Hauben, C. Rommel, and R. Cirillo (2007)
J. Pharmacol. Exp. Ther. 322, 923-930
   Abstract »    Full Text »    PDF »
PI3K{gamma} Is Required for PDE4, not PDE3, Activity in Subcellular Microdomains Containing the Sarcoplasmic Reticular Calcium ATPase in Cardiomyocytes.
B.-G. Kerfant, D. Zhao, I. Lorenzen-Schmidt, L. S. Wilson, S. Cai, S. R. W. Chen, D. H. Maurice, and P. H. Backx (2007)
Circ. Res. 101, 400-408
   Abstract »    Full Text »    PDF »
Phospholipase Cbeta Is Critical for T Cell Chemotaxis.
T. L. Bach, Q.-M. Chen, W. T. Kerr, Y. Wang, L. Lian, J. K. Choi, D. Wu, M. G. Kazanietz, G. A. Koretzky, S. Zigmond, et al. (2007)
J. Immunol. 179, 2223-2227
   Abstract »    Full Text »    PDF »
Leukocyte PI3K{gamma} and PI3K{delta} have temporally distinct roles for leukocyte recruitment in vivo.
L. Liu, K. D. Puri, J. M. Penninger, and P. Kubes (2007)
Blood 110, 1191-1198
   Abstract »    Full Text »    PDF »
Angiotensin II-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice.
G. Y. Oudit, Z. Kassiri, M. P. Patel, M. Chappell, J. Butany, P. H. Backx, R. G. Tsushima, J. W. Scholey, R. Khokha, and J. M. Penninger (2007)
Cardiovasc Res 75, 29-39
   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