ArticleThe Biochemical journal1996
The differential regulation of cyclic AMP by sphingomyelin-derived lipids and the modulation of sphingolipid-stimulated extracellular signal regulated kinase-2 in airway smooth muscle.
Article in The Biochemical journal, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 55 citations in OpenAlex.
- Integrative genetics-metabolomics analysis of infant bronchiolitis-childhood asthma link: A multicenter prospective study.Frontiers in immunology · 2022Article
- Sphingosine-1-phosphate induces islet β-cell proliferation and decreases cell apoptosis in high-fat diet/streptozotocin diabetic mice.Experimental and therapeutic medicine · 2019Article
- Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: challenges for SphK as an oncotarget.Oncotarget · 2017Review
- Motility, survival, and proliferation.Comprehensive Physiology · 2012Review
- TLR4 and S1P receptors cooperate to enhance inflammatory cytokine production in human gingival epithelial cells.European journal of immunology · 2008Article
- Transient relaxation of rat mesenteric microvessels by ceramides.British journal of pharmacology · 2002Article
- Sphingosine 1-phosphate signalling in mammalian cells.The Biochemical journal · 2000Review
- Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle. Role of endothelial differentiation gene 1, c-Src tyrosine kinase and phosphoinositide 3-kinase.The Biochemical journal · 1999Article
- Dual actions of sphingosine-1-phosphate: extracellular through the Gi-coupled receptor Edg-1 and intracellular to regulate proliferation and survival.The Journal of cell biology · 1998Article
- The identification of DL-threo dihydrosphingosine and sphingosine as novel inhibitors of extracellular signal-regulated kinase signalling in airway smooth muscle.British journal of pharmacology · 1996Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
We report that sphingosine and short-chain ceramides activate adenylate cyclase and stimulate intracellular cyclic AMP formation in airway-smooth-muscle (ASM) cells. In each case, there is a conditional requirement for GTP-Gs alpha. Sphingosine utilizes a protein kinase C-dependent pathway to elicit activation of adenylate cyclase, whereas for short-chain ceramides the mechanism remains unidentified. In contrast, sphingosine phosphate inhibits Gs-stimulated cyclic AMP formation via a Gi-dependent mechanism. Therefore, the potential interconversion of sphingosine and sphingosine phosphate is a switch that can elicit reciprocal changes in cyclic AMP levels. This may have a significant impact upon the regulation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal specific kinase (JNK) by sphingolipids and may help to explain how growth factors that utilize these second messengers evoke pleiotropic responses such as proliferation and cell survival. In this context, short-chain ceramides are poor stimulators of ERKs in ASM cells, and sphingosine is inactive, whereas both sphingolipids are powerful activators of the JNK module. Activated JNK catalyses N-terminal phosphorylation of c-Jun, a kinase cascade that programmes growth arrest. Therefore, in blocking ceramide-stimulated ERK-2 activity, cyclic AMP may allow the ceramide-dependent activation of JNK to programme cells to opt out of the cell cycle. In contrast, sphingosine phosphate activates ERK-2, potentiates growth-factor-stimulated DNA synthesis and fails to activate JNK, indicating that its sequential formation from ceramide and sphingosine may commit cells to DNA synthesis. ERK-2 can be activated by both cyclic AMP-sensitive c-Raf-1 kinase-dependent and cyclic AMP-insensitive c-Raf-1 kinase-independent pathways in ASM cells. In this context, sphingosine phosphate activates ERK-2 exclusively via c-Raf-1 kinase. Sphingosine phosphate-stimulated ERK-2 activity is also abolished by pertussis toxin, indicating that c-Raf-1 kinase is activated via a Gi-dependent mechanism.
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