Sphingomyelin-derived lipids differentially regulate the extracellular signal-regulated kinase 2 (ERK-2) and c-Jun N-terminal kinase (JNK) signal cascades in airway smooth muscle

S Pyne, J Chapman, L Steele, N J Pyne

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Abstract

In ASM cells platelet-derived growth factor stimulates rapid transient sphingosine phosphate formation, the activation of extracellular signal-regulated kinase 2 (ERK-2), the phosphorylation of p70(56K), and a ninefold increase in DNA synthesis. In contrast, this growth factor fails to activate c-Jun N-terminal kinase (JNK). Based upon these findings, we have tested whether the sphingomyelin-derived sphingolipids play a role in growth factor signalling by assessing their effect on ERK-2, JNK, and p70(56K). We demonstrate that sphingosine phosphate induces the activation of ERK-2, is ineffective against JNK, and fails to induce the phosphorylation of p70(56K). The latter may explain why it is a poor mitogen when added directly to ASM cells. In contrast, sphingosine and cell-permeable ceramides elicit the prominent tyrosyl phosphorylation and activation of JNK, are poor stimulators of ERK-2, and do not induce the phosphorylation of p70(56K). Therefore, the specificity of signalling through either ERK-2 or JNK cascades may be determined by the rapid agonist-dependent interconversion of these sphingomyelin-derived lipids. This may also provide a dynamic mechanism that enables growth factors and cytokines to elicit pleiotropic cell responses, such as proliferation and cell survival. For instance, both ceramide and sphingosine will elicit growth arrest via activation of JNK, whereas sphingosine phosphate will potentiate growth-factor-stimulated DNA synthesis, a consequence of the activation of ERK-2, Furthermore, under certain conditions, sphingosine and ceramide stimulate cAMP formation, a negative modulator of cell growth, whereas sphingosine phosphate depresses cAMP, thereby enhancing its own growth-promoting properties. From these studies, it is evident that sphingosine phosphate displays a signalling profile that is consistent with it mediating part of the action of platelet-derived growth factor.
Original languageEnglish
Pages (from-to)819-826
Number of pages8
JournalEuropean Journal of Biochemistry
Volume237
Issue number3
DOIs
Publication statusPublished - 1 May 1996

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Sphingosine
Sphingomyelins
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Smooth Muscle
Muscle
Lipids
Phosphorylation
Chemical activation
Phosphates
Ceramides
Intercellular Signaling Peptides and Proteins
Platelet-Derived Growth Factor
Growth
Sphingolipids
DNA
Cell growth
Mitogens
Modulators
Cell Survival

Keywords

  • animals
  • calcium-calmodulin-dependent protein kinases
  • cells, cultured
  • ceramides
  • cyclic AMP
  • DNA
  • enzyme activation
  • extracellular space
  • guinea pigs
  • JNK mitogen-activated protein kinases
  • lysophospholipids
  • MAP kinase kinase 4
  • mitogen-activated protein kinase 1
  • mitogen-activated protein kinase kinases
  • muscle, smooth
  • phospholipase D
  • phosphorylation
  • platelet-derived growth factor
  • protein kinases
  • protein-serine-threonine kinases
  • protein-tyrosine kinases
  • respiratory muscles
  • ribosomal protein S6 kinases
  • signal transduction
  • sphingolipids
  • sphingomyelins
  • sphingosine

Cite this

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title = "Sphingomyelin-derived lipids differentially regulate the extracellular signal-regulated kinase 2 (ERK-2) and c-Jun N-terminal kinase (JNK) signal cascades in airway smooth muscle",
abstract = "In ASM cells platelet-derived growth factor stimulates rapid transient sphingosine phosphate formation, the activation of extracellular signal-regulated kinase 2 (ERK-2), the phosphorylation of p70(56K), and a ninefold increase in DNA synthesis. In contrast, this growth factor fails to activate c-Jun N-terminal kinase (JNK). Based upon these findings, we have tested whether the sphingomyelin-derived sphingolipids play a role in growth factor signalling by assessing their effect on ERK-2, JNK, and p70(56K). We demonstrate that sphingosine phosphate induces the activation of ERK-2, is ineffective against JNK, and fails to induce the phosphorylation of p70(56K). The latter may explain why it is a poor mitogen when added directly to ASM cells. In contrast, sphingosine and cell-permeable ceramides elicit the prominent tyrosyl phosphorylation and activation of JNK, are poor stimulators of ERK-2, and do not induce the phosphorylation of p70(56K). Therefore, the specificity of signalling through either ERK-2 or JNK cascades may be determined by the rapid agonist-dependent interconversion of these sphingomyelin-derived lipids. This may also provide a dynamic mechanism that enables growth factors and cytokines to elicit pleiotropic cell responses, such as proliferation and cell survival. For instance, both ceramide and sphingosine will elicit growth arrest via activation of JNK, whereas sphingosine phosphate will potentiate growth-factor-stimulated DNA synthesis, a consequence of the activation of ERK-2, Furthermore, under certain conditions, sphingosine and ceramide stimulate cAMP formation, a negative modulator of cell growth, whereas sphingosine phosphate depresses cAMP, thereby enhancing its own growth-promoting properties. From these studies, it is evident that sphingosine phosphate displays a signalling profile that is consistent with it mediating part of the action of platelet-derived growth factor.",
keywords = "animals, calcium-calmodulin-dependent protein kinases, cells, cultured, ceramides, cyclic AMP, DNA, enzyme activation, extracellular space, guinea pigs, JNK mitogen-activated protein kinases, lysophospholipids, MAP kinase kinase 4, mitogen-activated protein kinase 1, mitogen-activated protein kinase kinases, muscle, smooth, phospholipase D, phosphorylation, platelet-derived growth factor, protein kinases, protein-serine-threonine kinases, protein-tyrosine kinases, respiratory muscles, ribosomal protein S6 kinases, signal transduction, sphingolipids, sphingomyelins, sphingosine",
author = "S Pyne and J Chapman and L Steele and Pyne, {N J}",
year = "1996",
month = "5",
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doi = "10.1111/j.1432-1033.1996.0819p.x",
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journal = "European Journal of Biochemistry",
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TY - JOUR

T1 - Sphingomyelin-derived lipids differentially regulate the extracellular signal-regulated kinase 2 (ERK-2) and c-Jun N-terminal kinase (JNK) signal cascades in airway smooth muscle

AU - Pyne, S

AU - Chapman, J

AU - Steele, L

AU - Pyne, N J

PY - 1996/5/1

Y1 - 1996/5/1

N2 - In ASM cells platelet-derived growth factor stimulates rapid transient sphingosine phosphate formation, the activation of extracellular signal-regulated kinase 2 (ERK-2), the phosphorylation of p70(56K), and a ninefold increase in DNA synthesis. In contrast, this growth factor fails to activate c-Jun N-terminal kinase (JNK). Based upon these findings, we have tested whether the sphingomyelin-derived sphingolipids play a role in growth factor signalling by assessing their effect on ERK-2, JNK, and p70(56K). We demonstrate that sphingosine phosphate induces the activation of ERK-2, is ineffective against JNK, and fails to induce the phosphorylation of p70(56K). The latter may explain why it is a poor mitogen when added directly to ASM cells. In contrast, sphingosine and cell-permeable ceramides elicit the prominent tyrosyl phosphorylation and activation of JNK, are poor stimulators of ERK-2, and do not induce the phosphorylation of p70(56K). Therefore, the specificity of signalling through either ERK-2 or JNK cascades may be determined by the rapid agonist-dependent interconversion of these sphingomyelin-derived lipids. This may also provide a dynamic mechanism that enables growth factors and cytokines to elicit pleiotropic cell responses, such as proliferation and cell survival. For instance, both ceramide and sphingosine will elicit growth arrest via activation of JNK, whereas sphingosine phosphate will potentiate growth-factor-stimulated DNA synthesis, a consequence of the activation of ERK-2, Furthermore, under certain conditions, sphingosine and ceramide stimulate cAMP formation, a negative modulator of cell growth, whereas sphingosine phosphate depresses cAMP, thereby enhancing its own growth-promoting properties. From these studies, it is evident that sphingosine phosphate displays a signalling profile that is consistent with it mediating part of the action of platelet-derived growth factor.

AB - In ASM cells platelet-derived growth factor stimulates rapid transient sphingosine phosphate formation, the activation of extracellular signal-regulated kinase 2 (ERK-2), the phosphorylation of p70(56K), and a ninefold increase in DNA synthesis. In contrast, this growth factor fails to activate c-Jun N-terminal kinase (JNK). Based upon these findings, we have tested whether the sphingomyelin-derived sphingolipids play a role in growth factor signalling by assessing their effect on ERK-2, JNK, and p70(56K). We demonstrate that sphingosine phosphate induces the activation of ERK-2, is ineffective against JNK, and fails to induce the phosphorylation of p70(56K). The latter may explain why it is a poor mitogen when added directly to ASM cells. In contrast, sphingosine and cell-permeable ceramides elicit the prominent tyrosyl phosphorylation and activation of JNK, are poor stimulators of ERK-2, and do not induce the phosphorylation of p70(56K). Therefore, the specificity of signalling through either ERK-2 or JNK cascades may be determined by the rapid agonist-dependent interconversion of these sphingomyelin-derived lipids. This may also provide a dynamic mechanism that enables growth factors and cytokines to elicit pleiotropic cell responses, such as proliferation and cell survival. For instance, both ceramide and sphingosine will elicit growth arrest via activation of JNK, whereas sphingosine phosphate will potentiate growth-factor-stimulated DNA synthesis, a consequence of the activation of ERK-2, Furthermore, under certain conditions, sphingosine and ceramide stimulate cAMP formation, a negative modulator of cell growth, whereas sphingosine phosphate depresses cAMP, thereby enhancing its own growth-promoting properties. From these studies, it is evident that sphingosine phosphate displays a signalling profile that is consistent with it mediating part of the action of platelet-derived growth factor.

KW - animals

KW - calcium-calmodulin-dependent protein kinases

KW - cells, cultured

KW - ceramides

KW - cyclic AMP

KW - DNA

KW - enzyme activation

KW - extracellular space

KW - guinea pigs

KW - JNK mitogen-activated protein kinases

KW - lysophospholipids

KW - MAP kinase kinase 4

KW - mitogen-activated protein kinase 1

KW - mitogen-activated protein kinase kinases

KW - muscle, smooth

KW - phospholipase D

KW - phosphorylation

KW - platelet-derived growth factor

KW - protein kinases

KW - protein-serine-threonine kinases

KW - protein-tyrosine kinases

KW - respiratory muscles

KW - ribosomal protein S6 kinases

KW - signal transduction

KW - sphingolipids

KW - sphingomyelins

KW - sphingosine

U2 - 10.1111/j.1432-1033.1996.0819p.x

DO - 10.1111/j.1432-1033.1996.0819p.x

M3 - Article

VL - 237

SP - 819

EP - 826

JO - European Journal of Biochemistry

JF - European Journal of Biochemistry

SN - 0014-2956

IS - 3

ER -