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.


Sci. Signal., 9 September 2008
Vol. 1, Issue 36, p. ra3
[DOI: 10.1126/scisignal.1161577]


Editor's Summary

Unveiling p110β
Phosphatidylinositide 3-kinase (PI3K) signaling has been implicated in the response to insulin and various growth factors. However, the specific role of the β isoform of the PI3K catalytic subunit (p110β) has been unclear. Analysis of mouse mutants carrying a catalytically inactive form of p110β reveals that it possesses noncatalytic as well as catalytic functions. Moreover, its catalytic activity is involved in sustaining the response to insulin signaling and in mediating forms of breast cancer associated with oncogenic epidermal growth factor signaling.

Citation: E. Ciraolo, M. Iezzi, R. Marone, S. Marengo, C. Curcio, C. Costa, O. Azzolino, C. Gonella, C. Rubinetto, H. Wu, W. Dastrù, E. L. Martin, L. Silengo, F. Altruda, E. Turco, L. Lanzetti, P. Musiani, T. Rückle, C. Rommel, J. M. Backer, G. Forni, M. P. Wymann, E. Hirsch, Phosphoinositide 3-Kinase p110β Activity: Key Role in Metabolism and Mammary Gland Cancer but Not Development. Sci. Signal. 1, ra3 (2008).

Read the Full Text

p87 and p101 Subunits Are Distinct Regulators Determining Class IB Phosphoinositide 3-Kinase (PI3K) Specificity.
A. Shymanets, Prajwal, K. Bucher, S. Beer-Hammer, C. Harteneck, and B. Nurnberg (2013)
J. Biol. Chem. 288, 31059-31068
   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 »
G Protein-Coupled Receptor-Mediated Activation of p110{beta} by G{beta}{gamma} Is Required for Cellular Transformation and Invasiveness.
H. A. Dbouk, O. Vadas, A. Shymanets, J. E. Burke, R. S. Salamon, B. D. Khalil, M. O. Barrett, G. L. Waldo, C. Surve, C. Hsueh, et al. (2012)
Science Signaling 5, ra89
   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 »
Cannabinoids Induce Pancreatic {beta}-Cell Death by Directly Inhibiting Insulin Receptor Activation.
W. Kim, Q. Lao, Y.-K. Shin, O. D. Carlson, E. K. Lee, M. Gorospe, R. N. Kulkarni, and J. M. Egan (2012)
Science Signaling 5, ra23
   Abstract »    Full Text »    PDF »
Role and regulation of phosphatidylinositol 3-kinase {beta} in platelet integrin {alpha}2{beta}1 signaling.
A. Consonni, L. Cipolla, G. Guidetti, I. Canobbio, E. Ciraolo, E. Hirsch, M. Falasca, M. Okigaki, C. Balduini, and M. Torti (2012)
Blood 119, 847-856
   Abstract »    Full Text »    PDF »
Gastric Inhibitory Peptide Controls Adipose Insulin Sensitivity via Activation of cAMP-response Element-binding Protein and p110{beta} Isoform of Phosphatidylinositol 3-Kinase.
S. Mohammad, L. S. Ramos, J. Buck, L. R. Levin, F. Rubino, and T. E. McGraw (2011)
J. Biol. Chem. 286, 43062-43070
   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 »
Structural Basis for Activation and Inhibition of Class I Phosphoinositide 3-Kinases.
O. Vadas, J. E. Burke, X. Zhang, A. Berndt, and R. L. Williams (2011)
Science Signaling 4, re2
   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 »
The class IA phosphatidylinositol 3-kinase p110-{beta} subunit is a positive regulator of autophagy.
Z. Dou, M. Chattopadhyay, J.-A. Pan, J. L. Guerriero, Y.-P. Jiang, L. M. Ballou, Z. Yue, R. Z. Lin, and W.-X. Zong (2010)
J. Cell Biol. 191, 827-843
   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 »
A constitutively activated form of the p110{beta} isoform of PI3-kinase induces prostatic intraepithelial neoplasia in mice.
S. H. Lee, G. Poulogiannis, S. Pyne, S. Jia, L. Zou, S. Signoretti, M. Loda, L. C. Cantley, and T. M. Roberts (2010)
PNAS 107, 11002-11007
   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 »
Disulfiram Treatment Facilitates Phosphoinositide 3-Kinase Inhibition in Human Breast Cancer Cells In vitro and In vivo.
H. Zhang, D. Chen, J. Ringler, W. Chen, Q. C. Cui, S. P. Ethier, Q. P. Dou, and G. Wu (2010)
Cancer Res. 70, 3996-4004
   Abstract »    Full Text »    PDF »
Phosphoinositide 3-Kinase Pathway Activation in Phosphate and Tensin Homolog (PTEN)-deficient Prostate Cancer Cells Is Independent of Receptor Tyrosine Kinases and Mediated by the p110{beta} and p110{delta} Catalytic Subunits.
X. Jiang, S. Chen, J. M. Asara, and S. P. Balk (2010)
J. Biol. Chem. 285, 14980-14989
   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 »
Nuclear phosphoinositide 3-kinase {beta} controls double-strand break DNA repair.
A. Kumar, O. Fernandez-Capetillo, and A. C. Carrera (2010)
PNAS 107, 7491-7496
   Abstract »    Full Text »    PDF »
Deletion of the p110{beta} isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo.
V. Martin, J. Guillermet-Guibert, G. Chicanne, C. Cabou, M. Jandrot-Perrus, M. Plantavid, B. Vanhaesebroeck, B. Payrastre, and M.-P. Gratacap (2010)
Blood 115, 2008-2013
   Abstract »    Full Text »    PDF »
Essential Role of the p110{beta} Subunit of Phosphoinositide 3-OH Kinase in Male Fertility.
E. Ciraolo, F. Morello, R. M. Hobbs, F. Wolf, R. Marone, M. Iezzi, X. Lu, G. Mengozzi, F. Altruda, G. Sorba, et al. (2010)
Mol. Biol. Cell 21, 704-711
   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 »
Isoform-Specific Phosphoinositide 3-Kinase Inhibitors Exert Distinct Effects in Solid Tumors.
K. A. Edgar, J. J. Wallin, M. Berry, L. B. Lee, W. W. Prior, D. Sampath, L. S. Friedman, and M. Belvin (2010)
Cancer Res. 70, 1164-1172
   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 »
Genetic evidence for a predominant role of PI3K{beta} catalytic activity in ITAM- and integrin-mediated signaling in platelets.
I. Canobbio, L. Stefanini, L. Cipolla, E. Ciraolo, C. Gruppi, C. Balduini, E. Hirsch, and M. Torti (2009)
Blood 114, 2193-2196
   Abstract »    Full Text »    PDF »
Specific function of phosphoinositide 3-kinase beta in the control of DNA replication.
M. Marques, A. Kumar, A. M. Poveda, S. Zuluaga, C. Hernandez, S. Jackson, P. Pasero, and A. C. Carrera (2009)
PNAS 106, 7525-7530
   Abstract »    Full Text »    PDF »
PIK3CA and PIK3CB Inhibition Produce Synthetic Lethality when Combined with Estrogen Deprivation in Estrogen Receptor-Positive Breast Cancer.
R. J. Crowder, C. Phommaly, Y. Tao, J. Hoog, J. Luo, C. M. Perou, J. S. Parker, M. A. Miller, D. G. Huntsman, L. Lin, et al. (2009)
Cancer Res. 69, 3955-3962
   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