| First Author | Jones RG | Year | 2000 |
| Journal | J Exp Med | Volume | 191 |
| Issue | 10 | Pages | 1721-34 |
| PubMed ID | 10811865 | Mgi Jnum | J:62176 |
| Mgi Id | MGI:1858541 | Doi | 10.1084/jem.191.10.1721 |
| Citation | Jones RG, et al. (2000) Protein kinase B regulates T lymphocyte survival, nuclear factor kappaB activation, and Bcl-X(L) levels in vivo. J Exp Med 191(10):1721-34 |
| abstractText | The serine/threonine kinase protein kinase B (PKB)/Akt mediates cell survival in a variety of systems. We have generated transgenic mice expressing a constitutively active form of PKB (gag-PKB) to examine the effects of PKB activity on T lymphocyte survival. Thymocytes and mature T cells overexpressing gag-PKB displayed increased active PKB, enhanced viability in culture, and resistance to a variety of apoptotic stimuli. PKB activity prolonged the survival of CD4(+)CD8(+) double positive (DP) thymocytes in fetal thymic organ culture, but was unable to prevent antigen-induced clonal deletion of thymocytes expressing the major histocompatibility complex class I-restricted P14 T cell receptor (TCR). In mature T lymphocytes, PKB can be activated in response to TCR stimulation, and peptide-antigen-specific proliferation is enhanced in T cells expressing the gag-PKB transgene. Both thymocytes and T cells overexpressing gag-PKB displayed elevated levels of the antiapoptotic molecule Bcl-X(L). In addition, the activation of peripheral T cells led to enhanced nuclear factor (NF)-kappaB activation via accelerated degradation of the NF-kappaB inhibitory protein IkappaBalpha. Our data highlight a physiological role for PKB in promoting survival of DP thymocytes and mature T cells, and provide evidence for the direct association of three major survival molecules (PKB, Bcl-X(L), and NF-kappaB) in vivo in T lymphocytes. |
