Sphingosine prevents diacylglycerol signaling to mitogen-activated protein kinase in airway smooth muscle
Autor: | Deborah Tolan, Ann-Marie Conway, Nigel J. Pyne, Susan Pyne |
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Rok vydání: | 1997 |
Předmět: |
MAPK/ERK pathway
Diacylglycerol Kinase Physiology Butanols Guinea Pigs Palmitic Acid Phosphatidate Phosphatase Biology Bradykinin Diglycerides Phosphatidate chemistry.chemical_compound 1-Butanol Piperidines Sphingosine Animals Enzyme Inhibitors Protein kinase A Cells Cultured Protein Kinase C Protein kinase C Quinazolinones Diacylglycerol kinase Platelet-Derived Growth Factor Phospholipase C urogenital system Muscle Smooth Cell Biology Enzyme Activation Trachea Kinetics Phosphotransferases (Alcohol Group Acceptor) Biochemistry chemistry Calcium-Calmodulin-Dependent Protein Kinases Quinazolines Tetradecanoylphorbol Acetate lipids (amino acids peptides and proteins) Signal transduction Signal Transduction |
Zdroj: | American Journal of Physiology-Cell Physiology. 273:C928-C936 |
ISSN: | 1522-1563 0363-6143 |
Popis: | Because many agonists utilize diacylglycerol (DAG) to initiate nuclear transcriptional activity via protein kinase C (PKC), we have investigated whether sphingosine might counter DAG. Sphingosine inhibited PKC activity in an isolated airway smooth muscle cell lysate and prevented the activation of mitogen-activated protein kinase (MAPK) by platelet-derived growth factor, bradykinin, and phorbol 12-myristate 13-acetate in intact cells. MAPK activation in response to all the agonists involves PKC. The stimulation of [3H]palmitate-labeled cells with sphingosine, in the presence of butan-1-ol (0.3%, vol/vol), induced an increase in [3H]phosphatidate (PtdOH) but was without effect on [3H]DAG. [3H]PtdOH synthesis was inhibited, whereas [3H]DAG levels were increased in the presence of the DAG kinase inhibitor R-59949, indicating that sphingosine stimulates phospholipase C/DAG kinase. Recycling of DAG from PtdOH was prevented by a sphingosine-dependent inhibition of PtdOH phosphohydrolase-2 activity. In conclusion, the sphingosine-induced conversion of DAG to PtdOH may serve to optimize the effect of sphingosine on MAPK. This may account for the antiproliferative action of sphingosine. |
Databáze: | OpenAIRE |
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