The Rise and Fall of Ceramide and 1,2-Diacylglycerol (DAG): Modulation by Transforming Growth Factor-β1 (TGFβ1) and by Epidermal Growth Factor (EGF)

摘要: Transforming growth factor β1 (TGFβ1) increases the phosphorylation of epidermal (EGF) receptor and inhibits A431 cells, but mechanism TGFβ1 signaling is unknown. Recent studies from this other laboratories suggest a novel sphingomyelin signal transduction pathway (1–4). Ceramide, which generated by sphingomyelinase action, can be deacylated to sphingoid bases, are potential inhibitors protein kinase C (PKC). Ceramide appears have bioeffector properties. Cell-permeable ceramide analogs stimulate monocytic differentiation human leukemia (HL60) cells (1), as well EGF at Thr669 in epidermoid carcinoma (2). Further (3,4) demonstrate existence ceramide-activated (CAPK) that may mediate some these aspects. The present aim investigate TGFβl explore whether TGFβ1’s involves activation PKC 1,2-Diacylglycerol (DAG) and/or stimulation CAPK ceramide. DAG levels determined thin layer chromatography (TLC) after treatment with either or EGF. 100pM for 1 hr cellular contents 2-fold. 20nM 15 min decreases it 0.5-fold. reduced 2-fold almost unaffected To evaluate involvement components transduction, effects on activity studied. 20 nM membrane 0.5-fold controls, wheras 4-fold. Modulation paralled translocation enzyme between cytosol Western immunoblot analysis. These regulatory both sphingolipid phospholipid metabolisms could transmodulate mediated tranduction pathways.