Abstract
| Language | English |
|---|---|
| Pages | C928-936 |
| Number of pages | 8 |
| Journal | American Journal of Physiology |
| Volume | 273 |
| Issue number | 3 |
| Publication status | Published - Sep 1997 |
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Keywords
- 1-butanol
- animals
- bradykinin
- butanols
- calcium-calmodulin-dependent protein kinases
- cells, cultured
- diacylglycerol kinase
- diglycerides
- enzyme activation
- enzyme inhibitors
- guinea pigs
- kinetics
- muscle, smooth
- palmitic acid
- phosphatidate phosphatase
- phosphotransferases (alcohol group acceptor)
- piperidines
- platelet-derived growth factor
- protein kinase C
- quinazolines
- quinazolinones
- signal transduction
- sphingosine
- tetradecanoylphorbol acetate
- trachea
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Sphingosine prevents diacylglycerol signaling to mitogen-activated protein kinase in airway smooth muscle. / Tolan, D; Conway, A M; Pyne, N J; Pyne, S.
In: American Journal of Physiology, Vol. 273, No. 3 , 09.1997, p. C928-936.Research output: Contribution to journal › Article
TY - JOUR
T1 - Sphingosine prevents diacylglycerol signaling to mitogen-activated protein kinase in airway smooth muscle
AU - Tolan, D
AU - Conway, A M
AU - Pyne, N J
AU - Pyne, S
PY - 1997/9
Y1 - 1997/9
N2 - 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.
AB - 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.
KW - 1-butanol
KW - animals
KW - bradykinin
KW - butanols
KW - calcium-calmodulin-dependent protein kinases
KW - cells, cultured
KW - diacylglycerol kinase
KW - diglycerides
KW - enzyme activation
KW - enzyme inhibitors
KW - guinea pigs
KW - kinetics
KW - muscle, smooth
KW - palmitic acid
KW - phosphatidate phosphatase
KW - phosphotransferases (alcohol group acceptor)
KW - piperidines
KW - platelet-derived growth factor
KW - protein kinase C
KW - quinazolines
KW - quinazolinones
KW - signal transduction
KW - sphingosine
KW - tetradecanoylphorbol acetate
KW - trachea
M3 - Article
VL - 273
SP - C928-936
JO - American Journal of Physiology
T2 - American Journal of Physiology
JF - American Journal of Physiology
SN - 0002-9513
IS - 3
ER -