Expression of a mutated form of the p85α regulatory subunit of phosphatidylinositol 3-kinase in a Hodgkin's lymphoma-derived cell line (CO)
- 1 May 2002
- journal article
- Published by Springer Science and Business Media LLC in Leukemia
- Vol. 16 (5), 894-901
- https://doi.org/10.1038/sj.leu.2402484
Abstract
Phosphatidylinositol (PI) 3-kinase plays an important role in a variety of biological processes, including proliferation and apoptosis. PI3-kinase is a heterodimer consisting of an 85 kDa adapter protein (p85) containing one SH3 domain and two SH2 domains and a 110 kDa catalytic subunit (p110). Recently an oncogenic form of p85 named p65-PI3K lacking the C-terminal SH2 domain has been cloned from an irradiation-induced murine thymic lymphoma and transgenic mice expressing p65-PI3K in T lymphocytes develop a lymphoproliferative disorder. Here we describe the cloning of a C-terminal truncated form of p85 expressed in a human lymphoma cell line (CO) with a T cell phenotype derived from a patient with Hodgkin's disease. As a result of a frame-shift mutation at amino acid 636, p76 is lacking most of the C-terminal SH2 domain, but contains the inter-SH2 domain and is associated with an active form of PI3-kinase. A PI3-kinase-dependent constitutive activation of Akt was detected in CO cells which was only partially reduced after serum starvation. Treatment of CO cells with the PI3-kinase inhibitor wortmannin resulted in a concentration-dependent inhibition of cell proliferation associated with an increased number of apoptotic cells. This is the first detection of a mutated form of the p85 subunit of PI3-kinase in human hematopoietic cells further underlining a potential role of PI3-kinase/Akt signaling in human leukemogenesis.Keywords
This publication has 59 references indexed in Scilit:
- Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3)/Tec kinase-dependent calcium signaling pathway: a target for SHIP-mediated inhibitory signalsThe EMBO Journal, 1998
- THE ORIGIN OF HODGKIN AND REED/STERNBERG CELLS IN HODGKIN'S DISEASEAnnual Review of Immunology, 1998
- Modulation of interleukin-6 expression in Hodgkin and Reed-Sternberg cells by Epstein-Barr virusThe Journal of Pathology, 1997
- A Specific Product of Phosphatidylinositol 3-Kinase Directly Activates the Protein Kinase Akt through Its Pleckstrin Homology DomainMolecular and Cellular Biology, 1997
- Role of phosphatidylinositol 3-OH-kinase activity in the inhibition of apoptosis in haemopoietic cells: phosphatidylinositol 3-OH-kinase inhibitors reveal a difference in signalling between interleukin-3 and granulocyte-macrophage colony stimulating factorBiochemical Journal, 1995
- Phosphatidylinositol 3‐kinaseBioEssays, 1994
- Agonist-stimulated synthesis of phosphatidylinositol(3,4,5)-trisphosphate: A new intracellular signalling system?Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1993
- Phosphatidyl-inositol 3-kinase: a key enzyme in diverse signalling processesTrends in Cell Biology, 1992
- Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells.Proceedings of the National Academy of Sciences of the United States of America, 1991
- Heterogeneous expression of proto-oncogenes in Hodgkin's disease derived cell linesHematological Oncology, 1990