Cytokine Signaling

Dissecting Ceramide Signals

Science's STKE  14 Nov 2000:
Vol. 2000, Issue 58, pp. tw6
DOI: 10.1126/stke.2000.58.tw6

Treatment of cells with the inflammatory cytokine interleukin 1 causes synthesis of ceramide, a sphingolipid metabolite that mediates a signal that causes growth arrest. The growth arrest involves activation of the mitogen-activated protein (MAP) kinase family member SAPK (stress-activated protein kinase). Bourbon et al. analyzed the signaling connection between ceramide and the SAPK pathway in human embryonic kidney cells. Their experiments suggest that ceramide activates protein kinase C ζ(PKC-ζ) and causes association of PKC-ζ with SAPK and also with other members of the SAPK-activating MAP kinase cascade. The authors conclude that PKC-ζ mediates effects of ceramide to cause formation of a multiprotein complex that leads to activation of SAPK.

Bourbon, N.A., Yun, J., and Kester, M. (2000) Ceramide directly activates protein kinase C to regulate a stress-activated protein kinase signaling complex. J. Biol. Chem. 275: 35617-35623. [Full Text] [Abstract]