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

182 Citations (Scopus)

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

Fingerprint

1-Phosphatidylinositol 4-Kinase
Human Mammary Glands
Phosphatidylinositols
Metabolism
Phosphotransferases
Breast Neoplasms
Catalyst activity
Insulin
Guanine Nucleotides
Cell growth
Medical problems
Growth
G-Protein-Coupled Receptors
Insulin Resistance
Tumors
Catalytic Domain
Neoplasms
Carrier Proteins
Genes
Pharmacology

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Ciraolo, E., Iezzi, M., Marone, R., Marengo, S., Curcio, C., Costa, 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

Phosphoinositide 3-kinase p110β activity : Key role in metabolism and mammary gland cancer but not development. / Ciraolo, Elisa; Iezzi, Manuela; Marone, Romina; Marengo, Stefano; Curcio, Claudia; Costa, Carlotta; Azzolino, Ornella; Gonella, Cristiano; Rubinetto, Cristina; Wu, Haiyan; Dastrù, Walter; Martin, Erica L.; Silengo, Lorenzo; Altruda, Fiorella; Turco, Emilia; Lanzetti, Letizia; Musiani, Piero; Rückle, Thomas; Rommel, Christian; Backer, Jonathan M.; Forni, Guido; Wymann, Matthias P.; Hirsch, Emilio.

In: Science Signaling, Vol. 1, No. 36, ra3, 06.09.2008.

Research output: Contribution to journalArticle

Ciraolo, E, Iezzi, M, Marone, R, Marengo, S, Curcio, C, Costa, C, Azzolino, O, Gonella, C, Rubinetto, C, Wu, H, Dastrù, W, Martin, EL, Silengo, L, Altruda, F, Turco, E, Lanzetti, L, Musiani, P, Rückle, T, Rommel, C, Backer, JM, Forni, G, Wymann, MP & Hirsch, E 2008, 'Phosphoinositide 3-kinase p110β activity: Key role in metabolism and mammary gland cancer but not development', Science Signaling, vol. 1, no. 36, ra3. https://doi.org/10.1126/scisignal.1161577
Ciraolo, Elisa ; Iezzi, Manuela ; Marone, Romina ; Marengo, Stefano ; Curcio, Claudia ; Costa, Carlotta ; Azzolino, Ornella ; Gonella, Cristiano ; Rubinetto, Cristina ; Wu, Haiyan ; Dastrù, Walter ; Martin, Erica L. ; Silengo, Lorenzo ; Altruda, Fiorella ; Turco, Emilia ; Lanzetti, Letizia ; Musiani, Piero ; Rückle, Thomas ; Rommel, Christian ; Backer, Jonathan M. ; Forni, Guido ; Wymann, Matthias P. ; Hirsch, Emilio. / Phosphoinositide 3-kinase p110β activity : Key role in metabolism and mammary gland cancer but not development. In: Science Signaling. 2008 ; Vol. 1, No. 36.
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