Identification and characterization of a new oncogene derived from the regulatory subunit of phosphoinositide 3-kinase

Autor: Carlos Martínez-A, Julian Downward, Miguel Marcos, Pablo Rodriguez-Viciana, José Luis Torán, M. Luisa Gaspar, Stefan Wennström, Concepción Jiménez, Ana González-García, Emilio Diez, Victor Calvo, Sergio G. Copin, Juan Pablo Albar, Ana C. Carrera, Isabel Mérida, Cayetano von Kobbe, Luis R-Borlado, Esther Leonardo, David R. Jones
Rok vydání: 1998
Předmět:
Protein subunit
Recombinant Fusion Proteins
Mutant
Molecular Sequence Data
Nerve Tissue Proteins
Protein Serine-Threonine Kinases
Regulatory Sequences
Nucleic Acid

SH2 domain
Phosphatidylinositols
General Biochemistry
Genetics and Molecular Biology

Receptor tyrosine kinase
Interleukin 10 receptor
alpha subunit

Mice
Phosphatidylinositol 3-Kinases
Synaptotagmins
Proto-Oncogene Proteins
Animals
Amino Acid Sequence
Cloning
Molecular

Protein kinase A
Molecular Biology
Cell Line
Transformed

Phosphoinositide 3-kinase
Membrane Glycoproteins
General Immunology and Microbiology
biology
Base Sequence
General Neuroscience
Calcium-Binding Proteins
Wild type
3T3 Cells
Oncogenes
Cell Transformation
Neoplastic

Biochemistry
Enzyme Induction
Synaptotagmin I
COS Cells
biology.protein
Proto-Oncogene Proteins c-akt
Research Article
Zdroj: The EMBO journal. 17(3)
ISSN: 0261-4189
Popis: p85/p110 phosphoinositide 3-kinase (PI3K) is a heterodimer composed of a p85-regulatory and a p110-catalytic subunit, which is involved in a variety of cellular responses including cytoskeletal organization, cell survival and proliferation. We describe here the cloning and characterization of p65-PI3K, a mutant of the regulatory subunit of PI3K, which includes the initial 571 residues of the wild type p85alpha-protein linked to a region conserved in the eph tyrosine kinase receptor family. We demonstrate that this mutation, obtained from a transformed cell, unlike previously engineered mutations of the regulatory subunit, induces the constitutive activation of PI3K and contributes to cellular transformation. This report links the PI3K enzyme to mammalian tumor development for the first time.
Databáze: OpenAIRE