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.

摘要: We report that sphingosine and short-chain ceramides activate adenylate cyclase 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 protein kinase C-dependent pathway to elicit activation of cyclase, whereas the mechanism remains unidentified. contrast, phosphate inhibits Gs-stimulated via Gi-dependent mechanism. Therefore, potential interconversion switch can reciprocal changes levels. This may have significant impact upon regulation extracellular signal-regulated (ERK) c-Jun N-terminal specific (JNK) by sphingolipids help explain how growth factors utilize these second messengers evoke pleiotropic responses such as proliferation cell survival. this context, are poor stimulators ERKs ASM cells, inactive, both powerful activators JNK module. Activated catalyses phosphorylation c-Jun, cascade programmes arrest. blocking ceramide-stimulated ERK-2 activity, allow ceramide-dependent programme cells opt out cycle. activates ERK-2, potentiates growth-factor-stimulated DNA synthesis fails JNK, indicating its sequential from ceramide commit synthesis. be activated AMP-sensitive c-Raf-1 kinase-dependent AMP-insensitive kinase-independent pathways exclusively kinase. phosphate-stimulated activity also abolished pertussis toxin,