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Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/33704

Title: Divergent roles for Ras and Rap in the activation of p38 mitogen-activated protein kinase by interleukin-1
Author: O'NEILL, LUKE ANTHONY JOHN
PALSSON, EVA
Sponsor: Health Research Board
Enterprise Ireland
European Union (EU)
Author's Homepage: http://people.tcd.ie/laoneill
Keywords: Biochemistry
Issue Date: 2000
Publisher: The American Society for Biochemistry and Molecular Biology
Citation: E. M. Palsson, M. Popoff, M. Thelestam and L. A. O'Neill ‘Divergent roles for Ras and Rap in the activation of p38 mitogen-activated protein kinase by interleukin-1’ in The Journal of Biological Chemistry, 275, (11), 2000, pp 7818-7825
Series/Report no.: The Journal of Biological Chemistry
275
11
Abstract: We have found that lethal toxin from Clostridium sordellii, which specifically inactivates the low molecular weight G proteins Ras, Rap, and Rac, inhibits the activation of p38 mitogen-activated protein kinase (MAPK) by interleukin-1 (IL-1) in EL4.NOB-1 cells and primary fibroblasts. The target protein involved appeared to be Ras, because transient transfections with dominant negative RasN17 inhibited p38 MAPK activation by IL-1. Furthermore, transfections of cells with constitutively active RasVHa-activated p38 MAPK. Further evidence for Ras involvement came from the observation that IL-1 caused a rapid activation of Ras in the cells and from the inhibitory effects of the Ras inhibitors manumycin A and damnacanthal. Toxin B from Clostridium difficile, which inactivates Rac, Cdc42, and Rho, was without effect. Dominant negative versions of Rac (RacN17) or Rap (Rap1AN17) did not inhibit the response. Intriguingly, transfection of cells with dominant negative Rap1AN17 activated p38 MAPK. Furthermore, constitutively active Rap1AV12 inhibited p38 MAPK activation by IL-1, consistent with Rap antagonizing Ras function. IL-1 also activated Rap in the cells, but with slower kinetics than Ras. Our studies therefore provide clear evidence using multiple approaches for Ras as a signaling component in the activation of p38 MAPK by IL-1, with Rap having an inhibitory effect.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/33704
Appears in Collections:Biochemistry (Scholarly Publications)

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