Phosphoinositide 3-Kinase p110β Activity: Key Role in Metabolism and Mammary Gland Cancer but Not Development

• DOI: 10.1126/scisignal.1161577
• Publication Date: 2008-09-24T00:13:46Z
• Authors: 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. Backer; Guido Forni; Matthias P. Wymann; Emilio Hirsch
• Keywords: P110α

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 PIK3CB gene) is not clear. Here, we show that mouse mutants expressing a catalytically inactive PIK3CB(K805R) mutant survived adulthood but showed growth retardation developed mild insulin resistance with age. Pharmacological genetic analyses revealed activity required for signaling downstream heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors as well sustain long-term signaling. In addition, mice were protected model ERBB2-driven tumor development. These findings indicate an unexpected role diabetes cancer, opening potential avenues therapeutic intervention.