title: The kinase PDK1 is essential for B-cell receptor mediated survival signaling.
abstract: 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.
authors: Department of Microbiology & Immunology, Columbia University, College of Physicians & Surgeons, New York, New York, United States of America. sgpark@gist.ac.kr
authors: Sung-Gyoo
authors: SG
authors: Park
authors: Meixiao
authors: M
authors: Long
authors: Jung-Ah
authors: JA
authors: Kang
authors: Woo-Seok
authors: WS
authors: Kim
authors: Cho-Rong
authors: CR
authors: Lee
authors: Sin-Hyeog
authors: SH
authors: Im
authors: Ian
authors: I
authors: Strickland
authors: Jan
authors: J
authors: Schulze-Luehrmann
authors: Matthew S
authors: MS
authors: Hayden
authors: Sankar
authors: S
authors: Ghosh
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; C000631433:Pdk1 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011947:Receptors, Antigen, B-Cell; D017346:Protein Serine-Threonine Kinases
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