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

• Published in: The EMBO journal Vol. 17; no. 3; pp. 743 - 753
• Main Authors: Jimenez, Concepción, Jones, David R., Rodríguez-Viciana, Pablo, Gonzalez-García, Ana, Leonardo, Esther, Wennström, Stefan, von Kobbe, Cayetano, Toran, Jose L., R-Borlado, Luis, Calvo, Victor, Copin, Sergio G., Albar, Juan P., Gaspar, M. Luisa, Diez, Emilio, Marcos, Miguel A. R., Downward, Julian, Martinez-A, Carlos, Mérida, Isabel, Carrera, Ana C.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.02.1998
• Subjects: 3T3 Cells; Amino Acid Sequence; Animals; Base Sequence; Calcium-Binding Proteins; Cell Line, Transformed; Cell Transformation, Neoplastic - metabolism; Cloning, Molecular; COS Cells; Enzyme Induction - genetics; Enzyme Induction - physiology; Membrane Glycoproteins - analysis; Membrane Glycoproteins - physiology; Mice; Molecular Sequence Data; mutants; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - physiology; Oncogenes - genetics; phosphatidylinositol 3-kinase; Phosphatidylinositol 3-Kinases - analysis; Phosphatidylinositol 3-Kinases - chemistry; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositols - metabolism; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - physiology; Regulatory Sequences, Nucleic Acid - genetics; Synaptotagmin I; Synaptotagmins; transformation
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/17.3.743

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 p85α‐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.