Premium
Phosphoinositide 3‐kinase inhibitor LY294002 but not serum withdrawal suppresses proliferation of murine embryonic stem cells
Author(s) -
Lianguzova Maria S.,
Chuykin Ilia A.,
Nordheim Alfred,
Pospelov Valery A.
Publication year - 2007
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2007.01.019
Subject(s) - ly294002 , phosphoinositide 3 kinase , embryonic stem cell , microbiology and biotechnology , pi3k/akt/mtor pathway , stem cell , kinase , chemistry , biology , signal transduction , biochemistry , gene
Mouse embryonic stem (mES) cells have short duration of their cell cycle and are capable of proliferating in the absence of growth factors. To find out which signaling pathways contribute to the regulation of the mES cell cycle, we used pharmacological inhibitors of MAP and PI3 kinase cascades. The MAP kinase inhibitors as well as serum withdrawal did not affect mES cell cycle distribution, whereas the inhibitor of PI3K activity, LY294002, induced accumulation of cells in G 1 phase followed by apoptotic cell death. Serum withdrawal also causes apoptosis, but it does not change the content and activity of cell cycle regulators. In contrast, in mES cells treated with LY294002, the activities of Cdk2 and E2F were significantly decreased. Interestingly, LY294002 had a much stronger effect on cell cycle distribution in low serum conditions, implying that serum can promote G 1 → S transition of mES cells by a LY294002‐resistant mechanism. Thus, proliferation of mES cells is maintained by at least two separate mechanisms: a LY294002‐sensitive pathway, which is active even in the absence of serum, and LY294002‐resistant, but serum‐dependent, pathway.