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Record W1966766732 · doi:10.1038/icb.2012.31

Phosphatidylinositol‐3 kinase activity in B cells is negatively regulated by <i>Lyn</i> tyrosine kinase

2012· article· en· W1966766732 on OpenAlexaff
Yuekang Xu, Nicholas D. Huntington, Kenneth W. Harder, Harshal Nandurkar, Margaret L. Hibbs, David M. Tarlinton

Bibliographic record

VenueImmunology and Cell Biology · 2012
Typearticle
Languageen
FieldMedicine
TopicChronic Lymphocytic Leukemia Research
Canadian institutionsUniversity of British Columbia
FundersNational Medical Research CouncilDunhill Medical TrustMedical Research CouncilNational Health and Medical Research CouncilState Government of VictoriaMenzies FoundationAustralian Government
KeywordsLYNFYNPhosphatidylinositolTyrosine kinaseTyrosine-protein kinase CSKKinasePI3K/AKT/mTOR pathwayCell biologySrc family kinasebreakpoint cluster regionProto-oncogene tyrosine-protein kinase SrcChemistryCancer researchSignal transductionBiologyMolecular biologyReceptorBiochemistrySH2 domain

Abstract

fetched live from OpenAlex

Phosphatidylinositol-3 kinase (PI3K) activity is essential for normal B-cell receptor (BCR)-mediated responses. To understand the mechanisms of PI3K regulation during B-cell activation, we performed a series of biochemical analysis on primary B cells, and found that activity of Src family tyrosine kinases (SFK) is crucial for the activation of PI3K following BCR ligation and this is regulated by the SFK Lyn. We show that the hyperresponsive phenotype of B cells lacking Lyn is predicated on significantly increased basal and inducible PI3K activity that correlates with the constitutive hypophosphorylation of PAG/Cbp (phosphoprotein associated with glycosphingolipid-enriched microdomains/Csk-binding protein), a concomitant reduction in bound Csk in Lyn(-/-) B cells and elevated levels of active Fyn. Regulating SFK activity may thus be a central mechanism by which Lyn regulates PI3K activity in B cells. This study defines the molecular connection between the BCR and PI3K and reveals this to be a point of Lyn-mediated regulation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.027
Threshold uncertainty score0.955

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.269
Teacher spread0.257 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations21
Published2012
Admission routes1
Has abstractyes

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