| First Author | Nix M | Year | 2000 |
| Journal | Cell Death Differ | Volume | 7 |
| Issue | 5 | Pages | 413-24 |
| PubMed ID | 10800075 | Mgi Jnum | J:62446 |
| Mgi Id | MGI:1858885 | Doi | 10.1038/sj.cdd.4400666 |
| Citation | Nix M, et al. (2000) Perturbation of membrane microdomains reduces mitogenic signaling and increases susceptibility to apoptosis after T cell receptor stimulation. Cell Death Differ 7(5):413-24 |
| abstractText | Acid sphingomyelinase-deficient (asmase-/-) mice generated by gene targeting abundantly store sphingomyelin in the reticuloendothelial system of liver, spleen, bone marrow, and in brain. Liver cells of asmase-/- mice accumulate sphingomyelin and glycosphingolipids in purified lipid bilayers of microsomes, Golgi, and the plasma membrane, but cholesterol is depleted in the plasma membrane. Detergent-insoluble glycolipid-enriched membrane microdomains (GEM) can be isolated from hepatocytes, embryonic fibroblasts, and splenocytes of wild-type, but not of asmase-/- mice, by sucrose gradient density centrifugation. Lck and other Src-family kinases are reduced in isopycnic fractions of asmase-/- splenocytes compared to GEM-containing fractions of wild-type cells. The proliferation of asmase-/- T lymphocytes is reduced, whereas their susceptibility to Fas-induced apoptosis is increased after T cell receptor (TCR) stimulation. TNF receptor I signaling remains unimpaired. The perturbation of GEM impairs tyrosine phosphorylation and, consequently, mitogenic signaling of the TCR. Reduced MAPK activity-dependent FLICE-like inhibitory protein (FLIP) expression in asmase-/- T lymphocytes increases their sensitivity towards Fas-mediated apoptosis. Cell Death and Differentiation (2000) 7, 413 - 424 |
