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

被引：194

作者：

Ciraolo, Elisa ^{[1
]}

Iezzi, Manuela ^{[2
]}

Marone, Romina ^{[3
]}

Marengo, Stefano ^{[1
]}

Curcio, Claudia ^{[4
]}

Costa, Carlotta ^{[1
]}

Azzolino, Ornella ^{[1
]}

Gonella, Cristiano ^{[1
]}

Rubinetto, Cristina ^{[1
]}

Wu, Haiyan ^{[5
]}

Dastru, Walter ^{[6
]}

Martin, Erica L. ^{[7
]}

Silengo, Lorenzo ^{[1
]}

Altruda, Fiorella ^{[1
]}

Turco, Emilia ^{[1
]}

Lanzetti, Letizia ^{[8
]}

Musiani, Piero ^{[2
]}

Rueckle, Thomas ^{[9
]}

Rommel, Christian ^{[9
]}

Backer, Jonathan M. ^{[5
]}

Forni, Guido ^{[4
]}

Wymann, Matthias P. ^{[3
]}

Hirsch, Emilio ^{[1
]}

机构：

[1] Univ Turin, Dept Genet Biol & Biochem, Ctr Mol Biotechnol, I-10126 Turin, Italy

[2] Univ G dAnnunzio, Aging Res Ctr, I-66013 Chieti, Italy

[3] Univ Basel, Dept Biomed, Inst Biochem & Genet, CH-4058 Basel, Switzerland

[4] Univ Turin, Dept Clin & Biol Sci, Ctr Mol Biotechnol, I-10126 Turin, Italy

[5] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA

[6] Univ Turin, Dept Chem, IFM, Mol Imaging Ctr, I-10126 Turin, Italy

[7] Univ Turin, Dept Anesthesia & Crit Care, I-10126 Turin, Italy

[8] Univ Turin, Dipartimento Sci Oncol, Ist Ric & Cura Canc, I-10060 Turin, Italy

[9] Merck Serono SA, Geneva Res Ctr, CH-1202 Geneva, Switzerland

来源：

SCIENCE SIGNALING | 2008年 / 1卷 / 36期

关键词：

D O I：

10.1126/scisignal.1161577

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：12

共 38 条

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