Phosphoinositide 3-Kinase p110 beta Activity: Key Role in Metabolism and Mammary Gland Cancer but Not Development

作者：Ciraolo Elisa; Iezzi Manuela; Marone Romina; Marengo Stefano; Curcio Claudia; Costa Carlotta; Azzolino Ornella; Gonella Cristiano; Rubinetto Cristina; Wu Haiyan; Dastru Walter; Martin Erica L; Silengo Lorenzo; Altruda Fiorella; Turco Emilia; Lanzetti Letizia; Musiani Piero; Rueckle Thomas; Rommel Christian; Backer Jonathan M; Forni Guido; Wymann Matthias P; Hirsch Emilio^*

来源：Science Signaling, 2008, 1(36): ra3.

DOI：10.1126/scisignal.1161577

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 p110 beta (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 p110 beta function revealed that p110 beta 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 p110 beta catalytic activity in diabetes and cancer, opening potential avenues for therapeutic intervention.

• 出版日期2008-9-9