RT Journal Article
SR Electronic
T1 Coactivation Leads to Survival
JF Science's STKE
JO Sci. STKE
FD American Association for the Advancement of Science
SP tw8
OP tw8
DO 10.1126/stke.2000.38.tw8
VO 2000
IS 38
YR 2000
UL http://stke.sciencemag.org/content/2000/38/tw8.abstract
AB Integration of multiple signals can control whether cells live or die. Activation of the glucorticoid receptor (GR) or the T cell receptor (TCR)/CD3 complex can both cause apoptosis of T cells in certain circumstances. However, when these two receptors are activated simultaneously, glucocorticoid-induced apoptosis can be blocked. Jamieson and Yamamoto used pharmacological inhibitors and/or expression of pathway-specific mutant proteins to study the pathways mediating this cross talk between the TCR/CD3 complex and the glucocorticoid receptor. In both immortalized T cells lacking Fas and primary T cell cultures, activation of the Ras-Raf-mitogen-activated protein kinase pathway by the TCR/CD3 complex inhibited glucocorticoid-stimulated apoptosis, but did not involve the phosphatidylinositol 3 kinase and Akt pathway. Another pathway that provided protection was the pathway from Ras to activation of another GTP exchange factor, Ral.GDP. The authors found that activation of the TCR/CD3 complex did not regulate turnover of GR, but rather regulated (increased or decreased) the transcriptional activity of the receptors in a promoter-specific manner. Jamieson, C.A.M., and Yamamoto, K.R. (2000) Crosstalk pathway for inhibition of glucocorticoid-induced apoptosis by T cell receptor signalling. Proc. Natl. Acad. Sci. U.S.A. 97: 7319-7324. [Abstract] [Full Text]