SPHINGOLIPID METABOLITES DIFFERENTIALLY REGULATE EXTRACELLULAR SIGNAL-REGULATED KINASE AND STRESS-ACTIVATED PROTEIN-KINASE CASCADES

Citation
E. Coroneos et al., SPHINGOLIPID METABOLITES DIFFERENTIALLY REGULATE EXTRACELLULAR SIGNAL-REGULATED KINASE AND STRESS-ACTIVATED PROTEIN-KINASE CASCADES, Biochemical journal, 316, 1996, pp. 13-17
Citations number
34
Categorie Soggetti
Biology
Journal title
ISSN journal
02646021
Volume
316
Year of publication
1996
Part
1
Pages
13 - 17
Database
ISI
SICI code
0264-6021(1996)316:<13:SMDRES>2.0.ZU;2-E
Abstract
The mitogen-activated protein kinase (MAPK) signalling pathway serves to translocate information from activated plasmamembrane receptors to initiate nuclear transcriptional events. This cascade has recently bee n subdivided into two analogous pathways: the extracellular signal-reg ulated kinase (ERK) cascade, which preferentially signals mitogenesis, and the stress-activated protein kinase (SAPK) cascade, which is link ed to growth arrest and/or cellular inflammation. In concurrent experi ments utilizing rat glomerular mesangial cells (MCs), we demonstrate t hat growth factors or sphingosine activate ERK but not SAPK. In contra st, inflammatory cytokines or cell-permeable ceramide analogues activa te SAPK but not ERK. Ceramide, but not sphingosine, induces interleuki n-6 secretion, a marker of an inflamed phenotype. Moreover, ceramide c an suppress growth factor- or sphingosine-induced ERK activation as we ll as proliferation. These studies implicate sphingolipid metabolites as opposing regulators of cell proliferation and inflammation through activation of separate kinase cascades.