ArticleMolecular and cellular biology2013
Dual phosphorylation of Btk by Akt/protein kinase b provides docking for 14-3-3ζ, regulates shuttling, and attenuates both tonic and induced signaling in B cells.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Differential regulatory effects of the N-terminal region in SYK-fusion kinases reveal unique activation-inducible nuclear translocation of ITK-SYK.Scientific reports · 2025Article
- BTKbase, Bruton Tyrosine Kinase Variant Database in X-Linked Agammaglobulinemia: Looking Back and Ahead.Human mutation · 2023Article
- Transcription factor TFII-I fine tunes innate properties of B lymphocytes.Frontiers in immunology · 2023Article
- Development of a novel Bruton's tyrosine kinase inhibitor that exerts anti-cancer activities potentiates response of chemotherapeutic agents in multiple myeloma stem cell-like cells.Frontiers in pharmacology · 2022Article
- The Serine/Threonine Protein Phosphatase 2A (PP2A) Regulates Syk Activity in Human Platelets.International journal of molecular sciences · 2020Article
- Regulation of p53 by the 14-3-3 protein interaction network: new opportunities for drug discovery in cancer.Cell death discovery · 2020Review
- Synergistic effect of ibrutinib and CD19 CAR-T cells on Raji cells in vivo and in vitro.Cancer science · 2020Article
- 14-3-3ζ binds to and stabilizes phospho-beclin 1Journal of cellular and molecular medicine · 2020Article
- Noncovalent inhibitors reveal BTK gatekeeper and auto-inhibitory residues that control its transforming activity.JCI insight · 2019Article
- 14-3-3ζ-A Novel Immunogen Promotes Inflammatory Cytokine Production.Frontiers in immunology · 2019Article
- Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes.BMC genomics · 2018Article
- 14-3-3ζ binds to hepatitis B virus protein X and maintains its protein stability in hepatocellular carcinoma cells.Cancer medicine · 2018Article
- The kinase activity of the channel-kinase protein TRPM7 regulates stability and localization of the TRPM7 channel in polarized epithelial cells.The Journal of biological chemistry · 2018Article
- Pitfalls of Combining Novel Agents in Lymphoma.Current treatment options in oncology · 2018Review
- Terminating B cell receptor signaling.Oncotarget · 2017Article
- Review
- ANKRD54 preferentially selects Bruton's Tyrosine Kinase (BTK) from a Human Src-Homology 3 (SH3) domain library.PloS one · 2017Article
- Substitution scanning identifies a novel, catalytically active ibrutinib-resistant BTK cysteine 481 to threonine (C481T) variant.Leukemia · 2017Article
- Targeting B-cell receptor signaling in leukemia and lymphoma: how and why?International journal of hematologic oncology · 2016Review
- B Cell Receptor Activation Predominantly Regulates AKT-mTORC1/2 Substrates Functionally Related to RNA Processing.PloS one · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bruton's tyrosine kinase (Btk) is crucial for B-lymphocyte activation and development. Mutations in the Btk gene cause X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Using tandem mass spectrometry, 14-3-3ζ was identified as a new binding partner and negative regulator of Btk in both B-cell lines and primary B lymphocytes. The activated serine/threonine kinase Akt/protein kinase B (PKB) phosphorylated Btk on two sites prior to 14-3-3ζ binding. The interaction sites were mapped to phosphoserine pS51 in the pleckstrin homology domain and phosphothreonine pT495 in the kinase domain. The double-alanine, S51A/T495A, replacement mutant failed to bind 14-3-3ζ, while phosphomimetic aspartate substitutions, S51D/T495D, caused enhanced interaction. The phosphatidylinositol 3-kinase (PI3-kinase) inhibitor LY294002 abrogated S51/T495 phosphorylation and binding. A newly characterized 14-3-3 inhibitor, BV02, reduced binding, as did the Btk inhibitor PCI-32765 (ibrutinib). Interestingly, in the presence of BV02, phosphorylation of Btk, phospholipase Cγ2, and NF-κB increased strongly, suggesting that 14-3-3 also regulates B-cell receptor (BCR)-mediated tonic signaling. Furthermore, downregulation of 14-3-3ζ elevated nuclear translocation of Btk. The loss-of-function mutant S51A/T495A showed reduced tyrosine phosphorylation and ubiquitination. Conversely, the gain-of-function mutant S51D/T495D exhibited intense tyrosine phosphorylation, associated with Btk ubiquitination and degradation, likely contributing to the termination of BCR signaling. Collectively, this suggests that Btk could become an important new candidate for the general study of 14-3-3-mediated regulation.
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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.