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.


Logo for

Science 297 (5583): 1031-1034

Copyright © 2002 by the American Association for the Advancement of Science

Impaired B and T Cell Antigen Receptor Signaling in p110&dgr; PI 3-Kinase Mutant Mice

Klaus Okkenhaug,1 Antonio Bilancio,1* Géraldine Farjot,1* Helen Priddle,2*dagger Sara Sancho,3 Emma Peskett,1 Wayne Pearce,1 Stephen E. Meek,2 Ashreena Salpekar,1 Michael D. Waterfield,14 Andrew J. H. Smith,2 Bart Vanhaesebroeck14ddagger

Class IA phosphoinositide 3-kinases (PI3Ks) are a family of p85/p110 heterodimeric lipid kinases that generate second messenger signals downstream of tyrosine kinases, thereby controlling cell metabolism, growth, proliferation, differentiation, motility, and survival. Mammals express three class IA catalytic subunits: p110alpha , p110beta , and p110delta . It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles. Mice expressing a catalytically inactive form of p110delta (p110delta D910A) were generated by gene targeting. Antigen receptor signaling in B and T cells was impaired and immune responses in vivo were attenuated in p110delta mutant mice. They also developed inflammatory bowel disease. These results reveal a selective role for p110delta in immunity.

1 Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK.
2 Gene Targeting Laboratory, Center for Genome Research, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JQ, UK.
3 Frimorfo, Rue du Musée 12, CH-1705 Fribourg, Switzerland.
4 Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
*   These authors contributed equally to this report.

dagger    Present address: Roslin Institute, Roslin, Midlothian, EH25 9PS, UK.

ddagger    To whom correspondence should be addressed. E-mail: bartvanh{at}

Innate PI3K p110{delta} Regulates Th1/Th17 Development and Microbiota-Dependent Colitis.
E. C. Steinbach, T. Kobayashi, S. M. Russo, S. Z. Sheikh, G. R. Gipson, S. T. Kennedy, J. K. Uno, Y. Mishima, L. B. Borst, B. Liu, et al. (2014)
J. Immunol. 192, 3958-3968
   Abstract »    Full Text »    PDF »
How will B-cell-receptor-targeted therapies change future CLL therapy?.
J. A. Jones and J. C. Byrd (2014)
Blood 123, 1455-1460
   Abstract »    Full Text »    PDF »
IL-21 Promotes CD4 T Cell Responses by Phosphatidylinositol 3-Kinase-Dependent Upregulation of CD86 on B Cells.
K. Attridge, R. Kenefeck, L. Wardzinski, O. S. Qureshi, C. J. Wang, C. Manzotti, K. Okkenhaug, and L. S. K. Walker (2014)
J. Immunol. 192, 2195-2201
   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 »
Can Cancer Drugs Treat Immunodeficiency?.
M. E. Conley and D. A. Fruman (2013)
Science 342, 814-815
   Abstract »    Full Text »    PDF »
Requirement for Rictor in homeostasis and function of mature B lymphoid cells.
K. Lee, L. Heffington, J. Jellusova, K. T. Nam, A. Raybuck, S. H. Cho, J. W. Thomas, R. C. Rickert, and M. Boothby (2013)
Blood 122, 2369-2379
   Abstract »    Full Text »    PDF »
Inhibition of the p110{alpha} isoform of PI 3-kinase stimulates nonfunctional tumor angiogenesis.
A. Soler, H. Serra, W. Pearce, A. Angulo, J. Guillermet-Guibert, L. S. Friedman, F. Vinals, H. Gerhardt, O. Casanovas, M. Graupera, et al. (2013)
J. Exp. Med. 210, 1937-1945
   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 »
Lipid phosphatases identified by screening a mouse phosphatase shRNA library regulate T-cell differentiation and Protein kinase B AKT signaling.
L. Guo, C. Martens, D. Bruno, S. F. Porcella, H. Yamane, S. M. Caucheteux, J. Zhu, and W. E. Paul (2013)
PNAS 110, E1849-E1856
   Abstract »    Full Text »    PDF »
Disparate Roles for STAT5 in Primary and Secondary CTL Responses.
D. M. Mitchell and M. A. Williams (2013)
J. Immunol. 190, 3390-3398
   Abstract »    Full Text »    PDF »
Cytokine-producing B cells as regulators of pathogenic and protective immune responses.
S. Fillatreau (2013)
Ann Rheum Dis 72, ii80-ii84
   Abstract »    Full Text »    PDF »
Coming full circle: 70 years of chronic lymphocytic leukemia cell redistribution, from glucocorticoids to inhibitors of B-cell receptor signaling.
J. A. Burger and E. Montserrat (2013)
Blood 121, 1501-1509
   Abstract »    Full Text »    PDF »
Selective Inhibition of Phosphoinositide 3-Kinase p110{alpha} Preserves Lymphocyte Function.
L. So, S. S. Yea, J. S. Oak, M. Lu, A. Manmadhan, Q. H. Ke, M. R. Janes, L. V. Kessler, J. M. Kucharski, L.-S. Li, et al. (2013)
J. Biol. Chem. 288, 5718-5731
   Abstract »    Full Text »    PDF »
PAQR3 Modulates Insulin Signaling by Shunting Phosphoinositide 3-Kinase p110{alpha} to the Golgi Apparatus.
X. Wang, L. Wang, L. Zhu, Y. Pan, F. Xiao, W. Liu, Z. Wang, F. Guo, Y. Liu, W. G. Thomas, et al. (2013)
Diabetes 62, 444-456
   Abstract »    Full Text »    PDF »
Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas.
E. Martin-Sanchez, S. M. Rodriguez-Pinilla, M. Sanchez-Beato, L. Lombardia, B. Dominguez-Gonzalez, D. Romero, L. Odqvist, P. Garcia-Sanz, M. B. Wozniak, G. Kurz, et al. (2013)
Haematologica 98, 57-64
   Abstract »    Full Text »    PDF »
Protein kinase N1, a cell inhibitor of Akt kinase, has a central role in quality control of germinal center formation.
T. Yasui, K. Sakakibara-Yada, T. Nishimura, K. Morita, S. Tada, G. Mosialos, E. Kieff, and H. Kikutani (2012)
PNAS 109, 21022-21027
   Abstract »    Full Text »    PDF »
PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells.
D. K. Finlay, E. Rosenzweig, L. V. Sinclair, C. Feijoo-Carnero, J. L. Hukelmann, J. Rolf, A. A. Panteleyev, K. Okkenhaug, and D. A. Cantrell (2012)
J. Exp. Med. 209, 2441-2453
   Abstract »    Full Text »    PDF »
Recycling endosome-dependent and -independent mechanisms for IL-10 secretion in LPS-activated macrophages.
A. C. Stanley, Z. Z. Lieu, A. A. Wall, J. Venturato, T. Khromykh, N. A. Hamilton, P. A. Gleeson, and J. L. Stow (2012)
J. Leukoc. Biol. 92, 1227-1239
   Abstract »    Full Text »    PDF »
Subnuclear cyclin D3 compartments and the coordinated regulation of proliferation and immunoglobulin variable gene repression.
S. E. Powers, M. Mandal, S. Matsuda, A. V. Miletic, M. H. Cato, A. Tanaka, R. C. Rickert, S. Koyasu, and M. R. Clark (2012)
J. Exp. Med. 209, 2199-2213
   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 »
FoxO-Dependent Regulation of Diacylglycerol Kinase {alpha} Gene Expression.
M. Martinez-Moreno, J. Garcia-Lievana, D. Soutar, P. Torres-Ayuso, E. Andrada, X.-P. Zhong, G. A. Koretzky, I. Merida, and A. Avila-Flores (2012)
Mol. Cell. Biol. 32, 4168-4180
   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 »
Loss of ATM kinase activity leads to embryonic lethality in mice.
J. A. Daniel, M. Pellegrini, B.-S. Lee, Z. Guo, D. Filsuf, N. V. Belkina, Z. You, T. T. Paull, B. P. Sleckman, L. Feigenbaum, et al. (2012)
J. Cell Biol. 198, 295-304
   Abstract »    Full Text »    PDF »
Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia.
J. R. Brown, M. Hanna, B. Tesar, L. Werner, N. Pochet, J. M. Asara, Y. E. Wang, P. dal Cin, S. M. Fernandes, C. Thompson, et al. (2012)
Clin. Cancer Res. 18, 3791-3802
   Abstract »    Full Text »    PDF »
Pten Loss in CD4 T Cells Enhances Their Helper Function but Does Not Lead to Autoimmunity or Lymphoma.
D. R. Soond, F. Garcon, D. T. Patton, J. Rolf, M. Turner, C. Scudamore, O. A. Garden, and K. Okkenhaug (2012)
J. Immunol. 188, 5935-5943
   Abstract »    Full Text »    PDF »
p110{delta} Phosphoinositide 3-Kinase Represses IgE Switch by Potentiating BCL6 Expression.
T.-t. Zhang, K. J. Makondo, and A. J. Marshall (2012)
J. Immunol. 188, 3700-3708
   Abstract »    Full Text »    PDF »
Functional CSF-1 receptors are located at the nuclear envelope and activated via the p110{delta} isoform of PI 3-kinase.
O. Zwaenepoel, N. Tzenaki, A. Vergetaki, A. Makrigiannakis, B. Vanhaesebroeck, and E. A. Papakonstanti (2012)
FASEB J 26, 691-706
   Abstract »    Full Text »    PDF »
The PI3K/PKB signaling module as key regulator of hematopoiesis: implications for therapeutic strategies in leukemia.
R. Polak and M. Buitenhuis (2012)
Blood 119, 911-923
   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 »
PI3K{delta} Inhibitors in Cancer: Rationale and Serendipity Merge in the Clinic.
D. A. Fruman and C. Rommel (2011)
Cancer Discovery 1, 562-572
   Abstract »    Full Text »    PDF »
The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia.
J. Hoellenriegel, S. A. Meadows, M. Sivina, W. G. Wierda, H. Kantarjian, M. J. Keating, N. Giese, S. O'Brien, A. Yu, L. L. Miller, et al. (2011)
Blood 118, 3603-3612
   Abstract »    Full Text »    PDF »
Identification of Mutations that Delay Somatic or Reproductive Aging of Caenorhabditis elegans.
S. E. Hughes, C. Huang, and K. Kornfeld (2011)
Genetics 189, 341-356
   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 »
Nuclear but Not Cytosolic Phosphoinositide 3-Kinase Beta Has an Essential Function in Cell Survival.
A. Kumar, J. Redondo-Munoz, V. Perez-Garcia, I. Cortes, M. Chagoyen, and A. C. Carrera (2011)
Mol. Cell. Biol. 31, 2122-2133
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 3-Kinase Isoform-Specific Effects in Airway Mesenchymal Cell Function.
L. M. Moir, T. Trian, Q. Ge, P. R. Shepherd, J. K. Burgess, B. G. G. Oliver, and J. L. Black (2011)
J. Pharmacol. Exp. Ther. 337, 557-566
   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 »
Role of Two Adaptor Molecules SLP-76 and LAT in the PI3K Signaling Pathway in Activated T Cells.
E. K. Shim, S. H. Jung, and J. R. Lee (2011)
J. Immunol. 186, 2926-2935
   Abstract »    Full Text »    PDF »
CAL-101, a p110{delta} selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability.
B. J. Lannutti, S. A. Meadows, S. E. M. Herman, A. Kashishian, B. Steiner, A. J. Johnson, J. C. Byrd, J. W. Tyner, M. M. Loriaux, M. Deininger, et al. (2011)
Blood 117, 591-594
   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 Activity in T Cells Regulates the Magnitude of the Germinal Center Reaction.
J. Rolf, S. E. Bell, D. Kovesdi, M. L. Janas, D. R. Soond, L. M. C. Webb, S. Santinelli, T. Saunders, B. Hebeis, N. Killeen, et al. (2010)
J. Immunol. 185, 4042-4052
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 3-kinase-{delta} inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals.
S. E. M. Herman, A. L. Gordon, A. J. Wagner, N. A. Heerema, W. Zhao, J. M. Flynn, J. Jones, L. Andritsos, K. D. Puri, B. J. Lannutti, et al. (2010)
Blood 116, 2078-2088
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-kinase {delta} regulates membrane fission of Golgi carriers for selective cytokine secretion.
P. C. Low, R. Misaki, K. Schroder, A. C. Stanley, M. J. Sweet, R. D. Teasdale, B. Vanhaesebroeck, F. A. Meunier, T. Taguchi, and J. L. Stow (2010)
J. Cell Biol. 190, 1053-1065
   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 »
B Cell Receptor Signaling: Picky About PI3Ks.
J. J. Limon and D. A. Fruman (2010)
Science Signaling 3, pe25
   Abstract »    Full Text »    PDF »
The PI3K Isoforms p110{alpha} and p110{delta} Are Essential for Pre-B Cell Receptor Signaling and B Cell Development.
F. Ramadani, D. J. Bolland, F. Garcon, J. L. Emery, B. Vanhaesebroeck, A. E. Corcoran, and K. Okkenhaug (2010)
Science Signaling 3, ra60
   Abstract »    Full Text »    PDF »
Activity of any class IA PI3K isoform can sustain cell proliferation and survival.
L. C. Foukas, I. M. Berenjeno, A. Gray, A. Khwaja, and B. Vanhaesebroeck (2010)
PNAS 107, 11381-11386
   Abstract »    Full Text »    PDF »
Human CD34-Derived Myeloid Dendritic Cell Development Requires Intact Phosphatidylinositol 3-Kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling.
L. van de Laar, M. Buitenhuis, F. M. Wensveen, H. L. A. Janssen, P. J. Coffer, and A. M. Woltman (2010)
J. Immunol. 184, 6600-6611
   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 »
Akt1 and Akt2 promote peripheral B-cell maturation and survival.
M. Calamito, M. M. Juntilla, M. Thomas, D. L. Northrup, J. Rathmell, M. J. Birnbaum, G. Koretzky, and D. Allman (2010)
Blood 115, 4043-4050
   Abstract »    Full Text »    PDF »
PI3K p110{delta} regulates T-cell cytokine production during primary and secondary immune responses in mice and humans.
D. R. Soond, E. Bjorgo, K. Moltu, V. Q. Dale, D. T. Patton, K. M. Torgersen, F. Galleway, B. Twomey, J. Clark, J. S. H. Gaston, et al. (2010)
Blood 115, 2203-2213
   Abstract »    Full Text »    PDF »
The p110{delta} Isoform of Phosphatidylinositol 3-Kinase Controls the Quality of Secondary Anti-Leishmania Immunity by Regulating Expansion and Effector Function of Memory T Cell Subsets.
D. Liu and J. E. Uzonna (2010)
J. Immunol. 184, 3098-3105
   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 Pleckstrin Homology Domain Adaptor Protein Bam32/DAPP1 Is Required for Germinal Center Progression.
T.-t. Zhang, M. Al-Alwan, and A. J. Marshall (2010)
J. Immunol. 184, 164-172
   Abstract »    Full Text »    PDF »
Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase.
M. Gigoux, J. Shang, Y. Pak, M. Xu, J. Choe, T. W. Mak, and W.-K. Suh (2009)
PNAS 106, 20371-20376
   Abstract »    Full Text »    PDF »
MAPK, Phosphatidylinositol 3-Kinase, and Mammalian Target of Rapamycin Pathways Converge at the Level of Ribosomal Protein S6 Phosphorylation to Control Metabolic Signaling in CD8 T Cells.
R. J. Salmond, J. Emery, K. Okkenhaug, and R. Zamoyska (2009)
J. Immunol. 183, 7388-7397
   Abstract »    Full Text »    PDF »
TAPP2 links phosphoinositide 3-kinase signaling to B-cell adhesion through interaction with the cytoskeletal protein utrophin: expression of a novel cell adhesion-promoting complex in B-cell leukemia.
J. L. Costantini, S. M. S. Cheung, S. Hou, H. Li, S. K. Kung, J. B. Johnston, J. A. Wilkins, S. B. Gibson, and A. J. Marshall (2009)
Blood 114, 4703-4712
   Abstract »    Full Text »    PDF »
Phosphoinositide (3,4,5)-Triphosphate Binding to Phosphoinositide-Dependent Kinase 1 Regulates a Protein Kinase B/Akt Signaling Threshold That Dictates T-Cell Migration, Not Proliferation.
C. Waugh, L. Sinclair, D. Finlay, J. R. Bayascas, and D. Cantrell (2009)
Mol. Cell. Biol. 29, 5952-5962
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-Kinase p110{delta} Regulates Natural Antibody Production, Marginal Zone and B-1 B Cell Function, and Autoantibody Responses.
C. A. Durand, K. Hartvigsen, L. Fogelstrand, S. Kim, S. Iritani, B. Vanhaesebroeck, J. L. Witztum, K. D. Puri, and M. R. Gold (2009)
J. Immunol. 183, 5673-5684
   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 »
The p110{delta} Isoform of Phosphatidylinositol 3-Kinase Controls Susceptibility to Leishmania major by Regulating Expansion and Tissue Homing of Regulatory T Cells.
D. Liu, T. Zhang, A. J. Marshall, K. Okkenhaug, B. Vanhaesebroeck, and J. E. Uzonna (2009)
J. Immunol. 183, 1921-1933
   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 »
Distinct roles for isoforms of the catalytic subunit of class-IA PI3K in the regulation of behaviour of murine embryonic stem cells.
E. Kingham and M. Welham (2009)
J. Cell Sci. 122, 2311-2321
   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 »
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 »
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 »
Distinct roles of class IA PI3K isoforms in primary and immortalised macrophages.
E. A. Papakonstanti, O. Zwaenepoel, A. Bilancio, E. Burns, G. E. Nock, B. Houseman, K. Shokat, A. J. Ridley, and B. Vanhaesebroeck (2008)
J. Cell Sci. 121, 4124-4133
   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 »
Leukemic challenge unmasks a requirement for PI3K{delta} in NK cell-mediated tumor surveillance.
E. Zebedin, O. Simma, C. Schuster, E. M. Putz, S. Fajmann, W. Warsch, E. Eckelhart, D. Stoiber, E. Weisz, J. A. Schmid, et al. (2008)
Blood 112, 4655-4664
   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 »
The p110{delta} of PI3K plays a critical role in NK cell terminal maturation and cytokine/chemokine generation.
H. Guo, A. Samarakoon, B. Vanhaesebroeck, and S. Malarkannan (2008)
J. Exp. Med. 205, 2419-2435
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-Kinase p110{beta} Activity: Key Role in Metabolism and Mammary Gland Cancer but Not Development.
E. Ciraolo, M. Iezzi, R. Marone, S. Marengo, C. Curcio, C. Costa, O. Azzolino, C. Gonella, C. Rubinetto, H. Wu, et al. (2008)
Science Signaling 1, ra3
   Abstract »    Full Text »    PDF »
PTEN-deficient cancers depend on PIK3CB.
S. Wee, D. Wiederschain, S.-M. Maira, A. Loo, C. Miller, R. deBeaumont, F. Stegmeier, Y.-M. Yao, and C. Lengauer (2008)
PNAS 105, 13057-13062
   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 »
Phosphatidylinositol 3-kinase signaling in mammalian preimplantation embryo development.
C. O'Neill (2008)
Reproduction 136, 147-156
   Abstract »    Full Text »    PDF »
Regulation of integrin activation through the B-cell receptor.
E. Arana, N. E. Harwood, and F. D. Batista (2008)
J. Cell Sci. 121, 2279-2286
   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 »
T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR.
S. Sauer, L. Bruno, A. Hertweck, D. Finlay, M. Leleu, M. Spivakov, Z. A. Knight, B. S. Cobb, D. Cantrell, E. O'Connor, et al. (2008)
PNAS 105, 7797-7802
   Abstract »    Full Text »    PDF »
Science amongst the vines: Meeting on Signalling Systems.
S. M. Pitson, G. J. Goodall, and M. A. Guthridge (2008)
EMBO Rep. 9, 425-428
   Full Text »    PDF »
Interleukin 13 Increases Contractility of Murine Tracheal Smooth Muscle by a Phosphoinositide 3-kinase p110{delta}-Dependent Mechanism.
H. S. M. Farghaly, I. S. Blagbrough, D. A. Medina-Tato, and M. L. Watson (2008)
Mol. Pharmacol. 73, 1530-1537
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-Kinases p110{alpha} and p110{beta} Regulate Cell Cycle Entry, Exhibiting Distinct Activation Kinetics in G1 Phase.
M. Marques, A. Kumar, I. Cortes, A. Gonzalez-Garcia, C. Hernandez, M. C. Moreno-Ortiz, and A. C. Carrera (2008)
Mol. Cell. Biol. 28, 2803-2814
   Abstract »    Full Text »    PDF »
PI3K is a negative regulator of IgE production.
T. Doi, K. Obayashi, T. Kadowaki, H. Fujii, and S. Koyasu (2008)
Int. Immunol. 20, 499-508
   Abstract »    Full Text »    PDF »
CD38 induces differentiation of immature transitional 2 B lymphocytes in the spleen.
J. C. Rodriguez-Alba, M. E. Moreno-Garcia, C. Sandoval-Montes, V. H. Rosales-Garcia, and L. Santos-Argumedo (2008)
Blood 111, 3644-3652
   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 »
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 »
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 »
The Effect of Deleting p110{delta} on the Phenotype and Function of PTEN-Deficient B Cells.
M. L. Janas, D. Hodson, Z. Stamataki, S. Hill, K. Welch, L. Gambardella, L. C. Trotman, P. P. Pandolfi, E. Vigorito, and M. Turner (2008)
J. Immunol. 180, 739-746
   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 »
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 »

To Advertise     Find Products

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