Phosphoinositide 3-kinase p110beta activity : key role in metabolism and mammary gland cancer but not development

Ciraolo, E. and Iezzi, M. and Marone, R. and Marengo, S. and Curcio, C. and Costa, C. and Azzolino, O. and Gonella, C. and Rubinetto, C. and Wu, H. and Dastrù, W. and Martin, E. L. and Silengo, L. and Altruda, F. and Turco, E. and Lanzetti, L. and Musiani, P. and Rückle, T. and Rommel, C. and Backer, J. M. and Forni, G. and Wymann, M. P. and Hirsch, E.. (2008) Phosphoinositide 3-kinase p110beta activity : key role in metabolism and mammary gland cancer but not development. Science signaling, Vol. 1, H. 36 , ra3.

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Official URL: http://edoc.unibas.ch/dok/A6004184

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The phosphoinositide 3-kinase (PI3K) pathway crucially controls metabolism and cell growth. Although different PI3K catalytic subunits are known to play distinct roles, the specific in vivo function of p110beta (the product of the PIK3CB gene) is not clear. Here, we show that mouse mutants expressing a catalytically inactive PIK3CB(K805R) mutant survived to adulthood but showed growth retardation and developed mild insulin resistance with age. Pharmacological and genetic analyses of p110beta function revealed that p110beta catalytic activity is required for PI3K signaling downstream of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors as well as to sustain long-term insulin signaling. In addition, PIK3CB(K805R) mice were protected in a model of ERBB2-driven tumor development. These findings indicate an unexpected role for p110beta catalytic activity in diabetes and cancer, opening potential avenues for therapeutic intervention.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Cancer- and Immunobiology (Wymann)
UniBasel Contributors:Wymann, Matthias P.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for the Advancement of Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Jul 2013 07:43
Deposited On:19 Jul 2013 07:41

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