RT Journal Article
SR Electronic
T1 Another Role for a Death Domain
JF Science's STKE
JO Sci. STKE
FD American Association for the Advancement of Science
SP tw4
OP tw4
DO 10.1126/stke.2000.50.tw4
VO 2000
IS 50
YR 2000
UL http://stke.sciencemag.org/content/2000/50/tw4.abstract
AB The protein PEA-15 is widely expressed and has a death effector domain (DED) in the NH2-terminal portion of the protein, which can bind to DEDs in pro-apoptotic proteins. Ramos et al. have studied PEA-15 in relation to its ability to activate Ras-mediated pathways leading to activation of extracellular signal-regulated kinase (ERK). Mutations in the DED of PEA-15 or deletion of the DED abolished PEA-15 activation of ERK; however, the DED of PEA-15 alone did not stimulate ERK in transfected cells. These data suggest that the DED of PEA-15 was necessary but not sufficient to induce ERK phosphorylation in transfected cells. The authors also investigated the signal transduction pathway from PEA-15 to ERK using cells transfected with dominant negative mutants of H-Ras, R-Ras, or Grb2, as well as pharmacological inhibitors of the ERK kinase, MEK. Their data suggest that, in transfected cells, PEA-15 stimulates ERK activity by activation of H-Ras downstream of Grb2 and upstream of MEK. Ramos, J.W., Hughes, P.E., Renshaw, M.W., Schwartz, M.A., Formstecher, E., Chneiweiss, H., and Ginsberg, M.H. (2000) Death effector domain protein PEA-15 potentiates Ras activation of extracellular signal receptor-activated kinase by an adhesion-independent mechanism. Mol. Biol. Cell 11: 2863-2872. [Abstract] [Full Text]