Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha.

Minghao Sun; Petra Hillmann; Bianca T. Hofmann; Jonathan R Hart; Peter K Vogt

Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha.

Standard

Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha. / Sun, Minghao; Hillmann, Petra; Hofmann, Bianca T.; Hart, Jonathan R; Vogt, Peter K.

in: P NATL ACAD SCI USA, Jahrgang 107, Nr. 35, 35, 2010, S. 15547-15552.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Sun, M, Hillmann, P, Hofmann, BT, Hart, JR & Vogt, PK 2010, 'Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha.', P NATL ACAD SCI USA, Jg. 107, Nr. 35, 35, S. 15547-15552. <http://www.ncbi.nlm.nih.gov/pubmed/20713702?dopt=Citation>

APA

Sun, M., Hillmann, P., Hofmann, B. T., Hart, J. R., & Vogt, P. K. (2010). Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha. P NATL ACAD SCI USA, 107(35), 15547-15552. [35]. http://www.ncbi.nlm.nih.gov/pubmed/20713702?dopt=Citation

Vancouver

Sun M, Hillmann P, Hofmann BT, Hart JR, Vogt PK. Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha. P NATL ACAD SCI USA. 2010;107(35):15547-15552. 35.

Bibtex

@article{01167df0c5f64dbca8a8dcb224a18e31,

title = "Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha.",

abstract = "Cancer-specific mutations in the iSH2 (inter-SH2) and nSH2 (N-terminal SH2) domains of p85alpha, the regulatory subunit of phosphatidylinositide 3-kinase (PI3K), show gain of function. They induce oncogenic cellular transformation, stimulate cellular proliferation, and enhance PI3K signaling. Quantitative determinations of oncogenic activity reveal large differences between individual mutants of p85alpha. The mutant proteins are still able to bind to the catalytic subunits p110alpha and p110beta. Studies with isoform-specific inhibitors of p110 suggest that expression of p85 mutants in fibroblasts leads exclusively to an activation of p110alpha, and p110alpha is the sole mediator of p85 mutant-induced oncogenic transformation. The characteristics of the p85 mutants are in agreement with the hypothesis that the mutations weaken an inhibitory interaction between p85alpha and p110alpha while preserving the stabilizing interaction between p85alpha iSH2 and the adapter-binding domain of p110alpha.",

keywords = "Animals, Humans, Cells, Cultured, Amino Acid Sequence, Base Sequence, Cell Proliferation, Blotting, Western, Cell Line, Transfection, Immunoprecipitation, Protein Binding, Cell Transformation, Neoplastic/*genetics, *Mutation, Thiazolidinediones/pharmacology, Fibroblasts/cytology/metabolism, Quinazolines/pharmacology, Chick Embryo, Adenine/analogs & derivatives/pharmacology, Catalytic Domain/genetics, Dioxoles/pharmacology, Morpholines/pharmacology, Neoplasms/enzymology/*genetics, Phosphatidylinositol 3-Kinases/antagonists & inhibitors/*genetics/metabolism, Protein Subunits/antagonists & inhibitors/genetics/metabolism, Pyrimidinones/pharmacology, Animals, Humans, Cells, Cultured, Amino Acid Sequence, Base Sequence, Cell Proliferation, Blotting, Western, Cell Line, Transfection, Immunoprecipitation, Protein Binding, Cell Transformation, Neoplastic/*genetics, *Mutation, Thiazolidinediones/pharmacology, Fibroblasts/cytology/metabolism, Quinazolines/pharmacology, Chick Embryo, Adenine/analogs & derivatives/pharmacology, Catalytic Domain/genetics, Dioxoles/pharmacology, Morpholines/pharmacology, Neoplasms/enzymology/*genetics, Phosphatidylinositol 3-Kinases/antagonists & inhibitors/*genetics/metabolism, Protein Subunits/antagonists & inhibitors/genetics/metabolism, Pyrimidinones/pharmacology",

author = "Minghao Sun and Petra Hillmann and Hofmann, {Bianca T.} and Hart, {Jonathan R} and Vogt, {Peter K}",

year = "2010",

language = "English",

volume = "107",

pages = "15547--15552",

journal = "P NATL ACAD SCI USA",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "35",

}

RIS

TY - JOUR

T1 - Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha.

AU - Sun, Minghao

AU - Hillmann, Petra

AU - Hofmann, Bianca T.

AU - Hart, Jonathan R

AU - Vogt, Peter K

PY - 2010

Y1 - 2010

N2 - Cancer-specific mutations in the iSH2 (inter-SH2) and nSH2 (N-terminal SH2) domains of p85alpha, the regulatory subunit of phosphatidylinositide 3-kinase (PI3K), show gain of function. They induce oncogenic cellular transformation, stimulate cellular proliferation, and enhance PI3K signaling. Quantitative determinations of oncogenic activity reveal large differences between individual mutants of p85alpha. The mutant proteins are still able to bind to the catalytic subunits p110alpha and p110beta. Studies with isoform-specific inhibitors of p110 suggest that expression of p85 mutants in fibroblasts leads exclusively to an activation of p110alpha, and p110alpha is the sole mediator of p85 mutant-induced oncogenic transformation. The characteristics of the p85 mutants are in agreement with the hypothesis that the mutations weaken an inhibitory interaction between p85alpha and p110alpha while preserving the stabilizing interaction between p85alpha iSH2 and the adapter-binding domain of p110alpha.

AB - Cancer-specific mutations in the iSH2 (inter-SH2) and nSH2 (N-terminal SH2) domains of p85alpha, the regulatory subunit of phosphatidylinositide 3-kinase (PI3K), show gain of function. They induce oncogenic cellular transformation, stimulate cellular proliferation, and enhance PI3K signaling. Quantitative determinations of oncogenic activity reveal large differences between individual mutants of p85alpha. The mutant proteins are still able to bind to the catalytic subunits p110alpha and p110beta. Studies with isoform-specific inhibitors of p110 suggest that expression of p85 mutants in fibroblasts leads exclusively to an activation of p110alpha, and p110alpha is the sole mediator of p85 mutant-induced oncogenic transformation. The characteristics of the p85 mutants are in agreement with the hypothesis that the mutations weaken an inhibitory interaction between p85alpha and p110alpha while preserving the stabilizing interaction between p85alpha iSH2 and the adapter-binding domain of p110alpha.

KW - Animals

KW - Humans

KW - Cells, Cultured

KW - Amino Acid Sequence

KW - Base Sequence

KW - Cell Proliferation

KW - Blotting, Western

KW - Cell Line

KW - Transfection

KW - Immunoprecipitation

KW - Protein Binding

KW - Cell Transformation, Neoplastic/genetics

KW - Mutation

KW - Thiazolidinediones/pharmacology

KW - Fibroblasts/cytology/metabolism

KW - Quinazolines/pharmacology

KW - Chick Embryo

KW - Adenine/analogs & derivatives/pharmacology

KW - Catalytic Domain/genetics

KW - Dioxoles/pharmacology

KW - Morpholines/pharmacology

KW - Neoplasms/enzymology/genetics

KW - Phosphatidylinositol 3-Kinases/antagonists & inhibitors/genetics/metabolism

KW - Protein Subunits/antagonists & inhibitors/genetics/metabolism

KW - Pyrimidinones/pharmacology