Sphingosine prevents diacylglycerol signaling to mitogen-activated protein kinase in airway smooth muscle

D Tolan, A M Conway, N J Pyne, S Pyne

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.
LanguageEnglish
PagesC928-936
Number of pages8
JournalAmerican Journal of Physiology
Volume273
Issue number3
Publication statusPublished - Sep 1997

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Sphingosine
Diglycerides
Mitogen-Activated Protein Kinases
Smooth Muscle
Diacylglycerol Kinase
Protein Kinase C
R 59949
Palmitates
Platelet-Derived Growth Factor
Recycling
Type C Phospholipases
Bradykinin
Phosphoric Monoester Hydrolases
Smooth Muscle Myocytes
Acetates

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

Cite this

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abstract = "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.",
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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 journalArticle

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 -