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. Backer; Guido Forni; Matthias P. Wymann; Emilio Hirsch

doi:10.1126/scisignal.1161577

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

Molecular Pharmacology

Research output: Contribution to journal › Article › peer-review

212 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 PIK3CB^K805R 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 language	English (US)
Article number	ra3
Journal	Science Signaling
Volume	1
Issue number	36
DOIs	https://doi.org/10.1126/scisignal.1161577
State	Published - Sep 6 2008

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1126/scisignal.1161577

Cite this

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), Article ra3. https://doi.org/10.1126/scisignal.1161577

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

@article{4a0a89774c974b3193e747f8f03ddb6f,

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

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.",

author = "Elisa Ciraolo and Manuela Iezzi and Romina Marone and Stefano Marengo and Claudia Curcio and Carlotta Costa and Ornella Azzolino and Cristiano Gonella and Cristina Rubinetto and Haiyan Wu and Walter Dastr{\`u} and Martin, {Erica L.} and Lorenzo Silengo and Fiorella Altruda and Emilia Turco and Letizia Lanzetti and Piero Musiani and Thomas R{\"u}ckle and Christian Rommel and Backer, {Jonathan M.} and Guido Forni and Wymann, {Matthias P.} and Emilio Hirsch",

year = "2008",

month = sep,

day = "6",

doi = "10.1126/scisignal.1161577",

language = "English (US)",

volume = "1",

journal = "Science Signaling",

issn = "1945-0877",

publisher = "American Association for the Advancement of Science",

number = "36",

}

TY - JOUR

T1 - Phosphoinositide 3-kinase p110β activity

T2 - Key role in metabolism and mammary gland cancer but not development

AU - Ciraolo, Elisa

AU - Iezzi, Manuela

AU - Marone, Romina

AU - Marengo, Stefano

AU - Curcio, Claudia

AU - Costa, Carlotta

AU - Azzolino, Ornella

AU - Gonella, Cristiano

AU - Rubinetto, Cristina

AU - Wu, Haiyan

AU - Dastrù, Walter

AU - Martin, Erica L.

AU - Silengo, Lorenzo

AU - Altruda, Fiorella

AU - Turco, Emilia

AU - Lanzetti, Letizia

AU - Musiani, Piero

AU - Rückle, Thomas

AU - Rommel, Christian

AU - Backer, Jonathan M.

AU - Forni, Guido

AU - Wymann, Matthias P.

AU - Hirsch, Emilio

PY - 2008/9/6

Y1 - 2008/9/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=55649084906&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55649084906&partnerID=8YFLogxK

U2 - 10.1126/scisignal.1161577

DO - 10.1126/scisignal.1161577

M3 - Article

C2 - 18780892

AN - SCOPUS:55649084906

SN - 1945-0877

VL - 1

JO - Science Signaling

JF - Science Signaling

IS - 36

M1 - ra3

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this