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.
Highlights
Phosphoinositide-dependent kinase 1 (PDK1) mediates signaling pathways activated by various cell surface receptors, and is important for cell metabolism, survival, and activation [1]
Upon B cell antigen receptor (BCR) stimulation, PDK1 is relocated to lipid rafts and is involved in activation of the NF-kB pathway, but not in the activation of JNK and p38 MAPK pathways
We found that PDK1 is involved in BCR-induced activation of the AKT pathway through phosphorylation of threonine 308 (T308) of AKT, while the other major phosphorylation site (S473) of AKT is not impacted by the inhibition of PDK1
Summary
Phosphoinositide-dependent kinase 1 (PDK1) mediates signaling pathways activated by various cell surface receptors, and is important for cell metabolism, survival, and activation [1]. PDK1 possesses a pleckstrin homology (PH) domain that binds to the second messenger PtdIns(3,4,5)P3 [1]. PDK1 is a wellcharacterized downstream signaling molecule of phosphoinositide 3-kinase (PI3K) [1], it has been suggested that PDK1 can phosphorylate substrate without binding to PtdIns(3,4,5)P3 [2]. PDK1 was initially identified as a kinase for AKT, and AKT remains the best-characterized PDK1 substrate [3,4]. AKT activity is regulated by phosphorylation at threonine 308 (T308) by PDK1 [4,5] and at serine 473 (S473) by mammalian target of rapamycin (mTOR) [6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
