Journal article
RasGRP1 confers the phorbol ester-sensitive phenotype to EL4 lymphoma cells
Molecular pharmacology, Vol.71(1), pp.314-322
01/2007
Handle:
https://hdl.handle.net/2376/111637
PMID: 17065239
Abstract
The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to the tumor promoter phorbol 12-myristate 13-acetate (PMA). In sensitive EL4 cells, PMA causes robust Erk mitogen-activated protein kinase activation that results in growth arrest. In resistant cells, PMA induces minimal Erk activation, without growth arrest. PMA stimulates IL-2 production in sensitive, but not resistant, cells. The role of RasGRP1, a PMA-activated guanine nucleotide exchange factor for Ras, in EL4 phenotype was examined. Endogenous RasGRP1 protein is expressed at much higher levels in sensitive than in resistant cells. PMA-induced Ras activation is observed in sensitive cells but not in resistant cells lacking Ras-GRP1. PMA induces down-regulation of RasGRP1 protein in sensitive cells but increases RasGRP1 in resistant cells. Transfection of RasGRP1 into resistant cells enhances PMA-induced Erk activation. In the reverse experiment, introduction of small interfering RNA (siRNA) for RasGRP1 suppresses PMA-induced Ras and Erk activations in sensitive cells. Sensitive cells incubated with siRNA for RasGRP1 exhibit the PMA-resistant phenotype, in that they are able to proliferate in the presence of PMA and do not secrete IL-2 when stimulated with PMA. These studies indicate that the PMA-sensitive phenotype, as previously defined for the EL4 cell line, is conferred by endogenous expression of RasGRP1 protein.
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Details
- Title
- RasGRP1 confers the phorbol ester-sensitive phenotype to EL4 lymphoma cells
- Creators
- Shujie Han - Department of Pharmaceutical Sciences, Washington State University, Pullman, WA 99164-6534, USAStewart M KnoeppMark A HallmanKathryn E Meier
- Publication Details
- Molecular pharmacology, Vol.71(1), pp.314-322
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- United States
- Grant note
- CA94144 / NCI NIH HHS CA58640 / NCI NIH HHS
- Identifiers
- 99900547709601842
- Language
- English
- Resource Type
- Journal article