Ceramide-dependent regulation of p42/p44 mitogen-activated protein kinase and c-Jun N-terminal-directed protein kinase in cultured airway smooth muscle cells

A M Conway, N J Pyne, S Pyne

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Previous studies have demonstrated that a number of biochemical actions of ceramide are mediated through protein kinase signalling pathways, such as p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) and c-Jun N-terminal directed protein kinase (JNK). Ceramide-activated protein kinases, such as the kinase suppressor of Ras (KSR) and protein kinase Czeta (PKCzeta), are involved in the regulation of c-Raf, which promotes sequential activation of MEK-1 and p42/p44 MAPK in mammalian cells. However, in cultured airway smooth muscle (ASM) cells, neither KSR nor PKCzeta are involved in the C2-ceramide (C2-Cer)-dependent activation of this kinase cascade. Instead, we found that C2-Cer utilises a novel pathway involving tyrosine kinases, phosphoinositide 3-kinase (PI3K) and conventional PKC isoform(s). We also found that despite its ability to stimulate p42/p44 MAPK, C2-Cer inhibited platelet-derived growth factor (PDGF)-stimulated DNA synthesis. The possibility that growth arrest could be mediated by JNK was discounted on the basis that PDGF, as well as ceramide, stimulated JNK in these cells. Therefore, growth arrest in response to ceramide is mediated by an alternative mechanism.
LanguageEnglish
Pages737-743
Number of pages7
JournalCellular Signalling
Volume12
Issue number11-12
DOIs
Publication statusPublished - Dec 2000

Fingerprint

Ceramides
Mitogen-Activated Protein Kinase 1
Protein Kinases
Smooth Muscle Myocytes
ras Proteins
Platelet-Derived Growth Factor
1-Phosphatidylinositol 4-Kinase
Mitogen-Activated Protein Kinase Kinases
Growth
Protein-Tyrosine Kinases
Protein Isoforms
Phosphotransferases
DNA
KSR-1 protein kinase

Keywords

  • animals
  • cell membrane permeability
  • cell survival
  • cells, cultured
  • ceramides
  • chromones
  • enzyme activation
  • guinea pigs
  • isoenzymes
  • JNK mitogen-activated protein kinases
  • lysophospholipids
  • mitogen-activated protein kinase 1
  • mitogen-activated protein kinase 3
  • mitogen-activated protein kinases
  • morpholines
  • muscle, smooth
  • phosphatidylinositol 3-kinases
  • platelet-derived growth factor
  • precipitin tests
  • protein kinase C
  • protein tyrosine phosphatases
  • protein-serine-threonine kinases
  • protein-tyrosine kinases
  • proto-oncogene proteins c-raf
  • respiratory system
  • signal transduction
  • sphingosine
  • tyrphostins

Cite this

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title = "Ceramide-dependent regulation of p42/p44 mitogen-activated protein kinase and c-Jun N-terminal-directed protein kinase in cultured airway smooth muscle cells",
abstract = "Previous studies have demonstrated that a number of biochemical actions of ceramide are mediated through protein kinase signalling pathways, such as p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) and c-Jun N-terminal directed protein kinase (JNK). Ceramide-activated protein kinases, such as the kinase suppressor of Ras (KSR) and protein kinase Czeta (PKCzeta), are involved in the regulation of c-Raf, which promotes sequential activation of MEK-1 and p42/p44 MAPK in mammalian cells. However, in cultured airway smooth muscle (ASM) cells, neither KSR nor PKCzeta are involved in the C2-ceramide (C2-Cer)-dependent activation of this kinase cascade. Instead, we found that C2-Cer utilises a novel pathway involving tyrosine kinases, phosphoinositide 3-kinase (PI3K) and conventional PKC isoform(s). We also found that despite its ability to stimulate p42/p44 MAPK, C2-Cer inhibited platelet-derived growth factor (PDGF)-stimulated DNA synthesis. The possibility that growth arrest could be mediated by JNK was discounted on the basis that PDGF, as well as ceramide, stimulated JNK in these cells. Therefore, growth arrest in response to ceramide is mediated by an alternative mechanism.",
keywords = "animals, cell membrane permeability, cell survival, cells, cultured, ceramides, chromones, enzyme activation, guinea pigs, isoenzymes, JNK mitogen-activated protein kinases, lysophospholipids, mitogen-activated protein kinase 1, mitogen-activated protein kinase 3, mitogen-activated protein kinases, morpholines, muscle, smooth, phosphatidylinositol 3-kinases, platelet-derived growth factor, precipitin tests, protein kinase C, protein tyrosine phosphatases, protein-serine-threonine kinases, protein-tyrosine kinases, proto-oncogene proteins c-raf, respiratory system, signal transduction, sphingosine, tyrphostins",
author = "Conway, {A M} and Pyne, {N J} and S Pyne",
year = "2000",
month = "12",
doi = "10.1016/S0898-6568(00)00119-4",
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TY - JOUR

T1 - Ceramide-dependent regulation of p42/p44 mitogen-activated protein kinase and c-Jun N-terminal-directed protein kinase in cultured airway smooth muscle cells

AU - Conway, A M

AU - Pyne, N J

AU - Pyne, S

PY - 2000/12

Y1 - 2000/12

N2 - Previous studies have demonstrated that a number of biochemical actions of ceramide are mediated through protein kinase signalling pathways, such as p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) and c-Jun N-terminal directed protein kinase (JNK). Ceramide-activated protein kinases, such as the kinase suppressor of Ras (KSR) and protein kinase Czeta (PKCzeta), are involved in the regulation of c-Raf, which promotes sequential activation of MEK-1 and p42/p44 MAPK in mammalian cells. However, in cultured airway smooth muscle (ASM) cells, neither KSR nor PKCzeta are involved in the C2-ceramide (C2-Cer)-dependent activation of this kinase cascade. Instead, we found that C2-Cer utilises a novel pathway involving tyrosine kinases, phosphoinositide 3-kinase (PI3K) and conventional PKC isoform(s). We also found that despite its ability to stimulate p42/p44 MAPK, C2-Cer inhibited platelet-derived growth factor (PDGF)-stimulated DNA synthesis. The possibility that growth arrest could be mediated by JNK was discounted on the basis that PDGF, as well as ceramide, stimulated JNK in these cells. Therefore, growth arrest in response to ceramide is mediated by an alternative mechanism.

AB - Previous studies have demonstrated that a number of biochemical actions of ceramide are mediated through protein kinase signalling pathways, such as p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) and c-Jun N-terminal directed protein kinase (JNK). Ceramide-activated protein kinases, such as the kinase suppressor of Ras (KSR) and protein kinase Czeta (PKCzeta), are involved in the regulation of c-Raf, which promotes sequential activation of MEK-1 and p42/p44 MAPK in mammalian cells. However, in cultured airway smooth muscle (ASM) cells, neither KSR nor PKCzeta are involved in the C2-ceramide (C2-Cer)-dependent activation of this kinase cascade. Instead, we found that C2-Cer utilises a novel pathway involving tyrosine kinases, phosphoinositide 3-kinase (PI3K) and conventional PKC isoform(s). We also found that despite its ability to stimulate p42/p44 MAPK, C2-Cer inhibited platelet-derived growth factor (PDGF)-stimulated DNA synthesis. The possibility that growth arrest could be mediated by JNK was discounted on the basis that PDGF, as well as ceramide, stimulated JNK in these cells. Therefore, growth arrest in response to ceramide is mediated by an alternative mechanism.

KW - animals

KW - cell membrane permeability

KW - cell survival

KW - cells, cultured

KW - ceramides

KW - chromones

KW - enzyme activation

KW - guinea pigs

KW - isoenzymes

KW - JNK mitogen-activated protein kinases

KW - lysophospholipids

KW - mitogen-activated protein kinase 1

KW - mitogen-activated protein kinase 3

KW - mitogen-activated protein kinases

KW - morpholines

KW - muscle, smooth

KW - phosphatidylinositol 3-kinases

KW - platelet-derived growth factor

KW - precipitin tests

KW - protein kinase C

KW - protein tyrosine phosphatases

KW - protein-serine-threonine kinases

KW - protein-tyrosine kinases

KW - proto-oncogene proteins c-raf

KW - respiratory system

KW - signal transduction

KW - sphingosine

KW - tyrphostins

U2 - 10.1016/S0898-6568(00)00119-4

DO - 10.1016/S0898-6568(00)00119-4

M3 - Article

VL - 12

SP - 737

EP - 743

JO - Cellular Signalling

T2 - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 11-12

ER -