Department of Microbiology & Immunology, Columbia University, College of Physicians & Surgeons, New York, New York, United States of America.
PLoS One. 2013;8(2):e55378. doi: 10.1371/journal.pone.0055378. Epub 2013 Feb 5.
Phosphoinositide-dependent kinase 1 (PDK1) plays an important role in integrating the T cell antigen receptor (TCR) and CD28 signals to achieve efficient NF-κB activation. PDK1 is also an important regulator of T cell development, mediating pre-TCR induced proliferation signals. However, the role of PDK1 in B cell antigen receptor (BCR) signaling and B cell development remains largely unknown. In this study we provide genetic evidence supporting the role of PDK1 in B cell survival. We found PDK1 is required for BCR mediated survival in resting B cells, likely through regulation of Foxo activation. PDK1-dependent signaling to NF-κB is not crucial to resting B cell viability. However, PDK1 is necessary for triggering NF-κB during B cell activation and is required for activated B cell survival. Together these studies demonstrate that PDK1 is essential for BCR-induced signal transduction to Foxo and NF-κB and is indispensable for both resting and activated B cell survival.
磷酸肌醇依赖的激酶 1（PDK1）在整合 T 细胞抗原受体（TCR）和 CD28 信号以实现有效的 NF-κB 激活方面发挥着重要作用。PDK1 也是 T 细胞发育的重要调节剂，介导 pre-TCR 诱导的增殖信号。然而，PDK1 在 B 细胞抗原受体（BCR）信号和 B 细胞发育中的作用在很大程度上仍然未知。在这项研究中，我们提供了支持 PDK1 在 B 细胞存活中发挥作用的遗传证据。我们发现 PDK1 是 BCR 介导的静止 B 细胞存活所必需的，可能通过调节 Foxo 的激活。PDK1 依赖的信号转导至 NF-κB 对于静止 B 细胞的存活并非至关重要。然而，PDK1 是在 B 细胞激活期间触发 NF-κB 所必需的，并且是激活的 B 细胞存活所必需的。这些研究共同表明，PDK1 对于 BCR 诱导的信号转导至 Foxo 和 NF-κB 是必不可少的，对于静止和激活的 B 细胞存活都是不可或缺的。
