Evidence map›Paper›PMID 24979759›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

PDK1 regulates B cell differentiation and homeostasis.

Gisele V Baracho, Matthew H Cato, Zilu Zhu, Olav R Jaren, Elias Hobeika, Michael Reth, Robert C Rickert

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Targeting enhancing myelin regeneration reverses cognitive deficits in a mouse model of intellectual disability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  3. A Microbiota- and IL-15-Dependent Innate-Like B Cell Progenitor Expressing E4BP4.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  12. AKT Isoforms in the Immune Response in Cancer.Current topics in microbiology and immunology · 2022
    Article
  13. Article
  14. PDK1 Is Required for Maintenance of CD4Journal of immunology (Baltimore, Md. : 1950) · 2021
    Article
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  18. Review
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Gisele V BarachoProgram on Immunity and Pathogenesis, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037; and.
Matthew H CatoProgram on Immunity and Pathogenesis, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037; and.
Zilu ZhuProgram on Immunity and Pathogenesis, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037; and.
Olav R JarenProgram on Immunity and Pathogenesis, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037; and.
Elias HobeikaBIOSS Centre for Biological Signalling Studies and Department of Molecular Immunology, Bio III, Faculty of Biology, University of Freiburg and Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Michael RethBIOSS Centre for Biological Signalling Studies and Department of Molecular Immunology, Bio III, Faculty of Biology, University of Freiburg and Max Planck Institute for Immunobiology and Epigenetics, 79108 Freiburg, Germany.
Robert C RickertProgram on Immunity and Pathogenesis, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037; and robert@sanfordburnham.org.
Sanford Burnham Prebys Medical Discovery Institute · USMax Planck Institute of Immunobiology and Epigenetics · DE

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
FUNCTION OF CD19 IN B CELL DEVELOPMENT/DIFFERENTIATIONR01AI041649 · NIAID · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI APGAR, JOHN R · 1998 to 2019
$7.0M
Phospholipid Signaling in B LymphocytesR01AI059447 · NIAID · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RICKERT, ROBERT C · 2005 to 2009
$3.8M
NCI NIH HHS P30 CA030199NIAID NIH HHS AI041649NIAID NIH HHS AI059447NIAID NIH HHS R01 AI041649NIAID NIH HHS R01 AI059447
6 · The paper itself

Abstract

Successful B cell differentiation and prevention of cell transformation depends on balanced and fine-tuned activation of cellular signaling pathways. The phosphatidyl inositol-3 kinase (PI3K) signaling pathway has emerged as a major regulator of B lymphocyte homeostasis and function. Phosphoinositide-dependent protein kinase-1 (PDK1) is the pivotal node in the PI3K pathway, regulating the stability and activity of downstream AGC kinases (including Akt, RSK, S6K, SGK, and PKC). Although the importance of PI3K activity in B cell differentiation is well documented, the role of PDK1 and other downstream effectors is underexplored. Here we used inducible and stage-specific gene targeting approaches to elucidate the role of PDK1 in early and peripheral B cell differentiation. PDK1 ablation enhanced cell cycle entry and apoptosis of IL-7-dependent pro-B cells, blocking Ig synthesis and B cell maturation. PDK1 also was essential for the survival and activation of peripheral B cells via regulation of PKC and Akt-dependent downstream effectors, such as GSK3α/β and Foxo1. We found that PDK1 deletion strongly impaired B cell receptor (BCR) signaling, but IL-4 costimulation was sufficient to restore BCR-induced proliferation. IL-4 also normalized PKCβ activation and hexokinase II expression in BCR-stimulated cells, suggesting that this signaling pathway can act independent of PDK1 to support B cell growth. In summary, our results demonstrate that PDK1 is indispensable for B cell survival, proliferation, and growth regulation.

Indexed as

3-Phosphoinositide-Dependent Protein KinasesAnimalsBlotting, WesternB-LymphocytesBone MarrowCell DifferentiationEnzyme-Linked Immunosorbent AssayFlow CytometryHomeostasisHumansMicePhosphatidylinositol 3-KinasesReceptors, Antigen, B-CellReceptors, CytokineStatistics, Nonparametric3-Phosphoinositide-Dependent Protein KinasesPdpk1 protein, mousePhosphatidylinositol 3-KinasesReceptors, Antigen, B-CellReceptors, Cytokine

Identifiers

PMID24979759
PMCPMC4084446
OpenAlexW2041352442

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.