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The Kinase PDK1 Is Essential for B-Cell Receptor Mediated Survival Signaling

Park, Sung-Gyoo; Long, Meixiao; Kang, Jung-Ah; Kim, Woo-Seok; Lee, Cho-Rong; Im, Sin-Hyeog; Strickland, Ian; Schulze-Luehrmann, Jan; Hayden, Matthew S.; Ghosh, Sankar

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.

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Academic Units
Microbiology and Immunology
Published Here
June 21, 2017