Phosphoinositide 3-kinase p110β activity: Key role in metabolism and mammary gland cancer but not development

Elisa Ciraolo, Manuela Iezzi, Romina Marone, Stefano Marengo, Claudia Curcio, Carlotta Costa, Ornella Azzolino, Cristiano Gonella, Cristina Rubinetto, Haiyan Wu, Walter Dastrù, Erica L. Martin, Lorenzo Silengo, Fiorella Altruda, Emilia Turco, Letizia Lanzetti, Piero Musiani, Thomas Rückle, Christian Rommel, Jonathan M. BackerGuido Forni, Matthias P. Wymann, Emilio Hirsch

Research output: Contribution to journalArticle

185 Scopus citations

Abstract

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 p110β (the product of the PIK3CB gene) is not clear. Here, we show that mouse mutants expressing a catalytically inactive PIK3CBK805R mutant survived to adulthood but showed growth retardation and developed mild insulin resistance with age. Pharmacological and genetic analyses of p110β function revealed that p110β 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 p110β catalytic activity in diabetes and cancer, opening potential avenues for therapeutic intervention. 10.1126/scisignal.1161577.

Original languageEnglish (US)
Article numberra3
JournalScience Signaling
Volume1
Issue number36
DOIs
StatePublished - Sep 6 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ciraolo, E., Iezzi, M., Marone, R., Marengo, S., Curcio, C., Costa, C., Azzolino, O., Gonella, C., Rubinetto, C., Wu, H., Dastrù, W., Martin, E. L., Silengo, L., Altruda, F., Turco, E., Lanzetti, L., Musiani, P., Rückle, T., Rommel, C., ... Hirsch, E. (2008). Phosphoinositide 3-kinase p110β activity: Key role in metabolism and mammary gland cancer but not development. Science Signaling, 1(36), [ra3]. https://doi.org/10.1126/scisignal.1161577