Starlets Diana, Gore Yael, Binsky Inbal, Haran Michal, Harpaz Nurit, Shvidel Lev, Becker-Herman Shirly, Berrebi Alain, Shachar Idit
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel 76100.
Blood. 2006 Jun 15;107(12):4807-16. doi: 10.1182/blood-2005-11-4334. Epub 2006 Feb 16.
CD74 is an integral membrane protein that was thought to function mainly as an MHC class II chaperone. However, CD74 was recently shown to have a role as an accessory-signaling molecule. Our studies demonstrated that CD74 regulates B-cell differentiation by inducing a pathway leading to the activation of transcription mediated by the NF-kappaB p65/RelA homodimer and its coactivator, TAF(II)105. Here, we show that CD74 stimulation with anti-CD74 antibody leads to an induction of a signaling cascade resulting in NF-kappaB activation, entry of the stimulated cells into the S phase, elevation of DNA synthesis, cell division, and augmented expression of BCL-X(L). These studies therefore demonstrate that surface CD74 functions as a survival receptor.
CD74是一种整合膜蛋白，曾被认为主要作为MHC II类分子伴侣发挥作用。然而，最近研究表明CD74具有辅助信号分子的作用。我们的研究证明，CD74通过诱导一条导致由NF-κB p65/RelA同二聚体及其辅激活因子TAF(II)105介导的转录激活的信号通路来调节B细胞分化。在此，我们发现用抗CD74抗体刺激CD74会导致信号级联反应的诱导，从而导致NF-κB激活、受刺激细胞进入S期、DNA合成增加、细胞分裂以及BCL-X(L)表达增强。因此，这些研究证明表面CD74作为一种生存受体发挥作用。
