Ceramide-dependent regulation of p42/p44 mitogen-activated protein kinase and c-Jun N-terminal-directed protein kinase in cultured airway smooth muscle cells
| Autor: | Nigel J. Pyne, Susan Pyne, Ann-Marie Conway |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
endocrine system
Cell Membrane Permeability Cell Survival Morpholines Guinea Pigs Respiratory System Mitogen-activated protein kinase kinase Protein Serine-Threonine Kinases Ceramides environment and public health MAP2K7 Phosphatidylinositol 3-Kinases Sphingosine Animals ASK1 c-Raf Cells Cultured Protein Kinase C Phosphoinositide-3 Kinase Inhibitors Mitogen-Activated Protein Kinase 1 Platelet-Derived Growth Factor Mitogen-Activated Protein Kinase 3 MAP kinase kinase kinase biology Chemistry Cyclin-dependent kinase 2 JNK Mitogen-Activated Protein Kinases Muscle Smooth Cell Biology Protein-Tyrosine Kinases Tyrphostins Protein kinase R Precipitin Tests Cell biology Enzyme Activation Isoenzymes Proto-Oncogene Proteins c-raf Chromones biology.protein Quinazolines Cyclin-dependent kinase 9 biological phenomena cell phenomena and immunity Lysophospholipids Mitogen-Activated Protein Kinases Protein Tyrosine Phosphatases Signal Transduction |
| Zdroj: | Cellular signalling. 12(11-12) |
| ISSN: | 0898-6568 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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