Tetradecanoyl phorbol acetate-induced microtubule reorganization is required for sustained mitogen-activated protein kinase activation and morphological differentiation of U937 cells
| Autor: | R D, Whelan, S C, Kiley, P J, Parker |
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| Rok vydání: | 1999 |
| Předmět: |
Flavonoids
Mitogen-Activated Protein Kinase 1 Time Factors Reverse Transcriptase Polymerase Chain Reaction Nocodazole Blotting Western Cell Differentiation U937 Cells Microtubules Precipitin Tests Gene Expression Regulation Calcium-Calmodulin-Dependent Protein Kinases Humans Tetradecanoylphorbol Acetate Cloning Molecular Enzyme Inhibitors |
| Zdroj: | Cell growthdifferentiation : the molecular biology journal of the American Association for Cancer Research. 10(4) |
| ISSN: | 1044-9523 |
| Popis: | Investigation of 12-tetradecanoyl phorbol 13-acetate (TPA)-resistant U937 cell clones has demonstrated that the normal sustained p42 mitogen-activated protein kinase (p42MAPK) activation produced by TPA treatment is absent. This is shown to be due to the inability of TPA to maintain activation of MAP/extracellular signal-regulated kinase kinase (MEK) and cRaf1. A direct relationship between sustained p42MAPK activation and differentiation is provided by the demonstration that blockade of MEK activation by PD098059 prevents TPA-induced morphological differentiation of wild type U937 cells. Using TPA-resistant clones, an involvement of microtubule reorganization and granule release is demonstrated by the ability of the microtubule depolymerizing agent nocodazole, to promote sustained p42MAPK activation in the presence of TPA. This response correlates with the lack of TPA-induced microtubule reorganization in these clones and the ability of nocodazole to partially bypass resistance to TPA. The results demonstrate a causal link between protein kinase C-dependent microtubule reorganization, sustained p42MAPK activation, and the induction of differentiation in U937 cells. |
| Databáze: | OpenAIRE |
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