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Cross‐talk between the PI3K/Akt and Raf/Erk Pathways in EL4 Cells
Author(s) -
Han Shujie,
Meier Kathryn E.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a794-c
Subject(s) - mapk/erk pathway , protein kinase b , pi3k/akt/mtor pathway , ly294002 , phosphorylation , microbiology and biotechnology , chemistry , cancer research , biology , signal transduction
The phosphoinositide 3‐kinase (PI3K)/Akt pathway is central to the control of cell growth, proliferation, and survival, as is the Ras/Raf/Erk pathway. In this study, we used a series of EL4 lymphoma cell lines to test the hypothesis that cross‐talk between the Akt and Erk pathways influences Erk activation profiles. Phorbol ester (PMA)‐sensitive EL4 cells (e.g., WT2) express RasGRP and show high levels of PMA‐induced Erk activation. We have previously shown that RasGRP, a phorbol ester‐activated Ras GEF, confers the PMA‐sensitive phenotype. However, although both PMA‐resistant (e.g., V7) and intermediate (e.g., V3) EL4 cells lack RasGRP, PMA‐induced Erk phosphorylation is higher in V3 than that in V7. We found that basal Akt phosphorylation is high in V7, but very low in WT2. Basal phospho‐Akt in intermediate cells (V3) is intermediate between WT2 and V7. Akt phosphorylation can be blocked by the PI3K inhibitor, LY294002. PMA‐induced Raf and Erk phosphorylations were enhanced by LY294002 in all cell types (WT2, V3 and V7), indicating that PI3K/Akt activation is inhibitory to Erk activation. Despite enhancement by LY294002, PMA‐induced Raf/Erk activation in V3 and V7 remained weaker than that seen in WT2. In summary, the results suggest that lack of RasGRP, combined with high basal activity of PI3K/Akt, is responsible for the low level of PMA‐induced Raf/Erk activation in PMA‐resistant EL4 cells. (NIH CA094144‐01)