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Record W2785293290 · doi:10.1073/pnas.1714446115

Context-dependent functions of angiopoietin 2 are determined by the endothelial phosphatase VEPTP

2018· article· en· W2785293290 on OpenAlexafffund
Tomokazu Souma, Benjamin R. Thomson, Stefan Heinen, Isabel Anna Carota, Shinji Yamaguchi, Tuncer Onay, Pan Liu, Asish K. Ghosh, Chengjin Li, Vera Eremina, Young‐Kwon Hong, Aris N. Economides, Dietmar Vestweber, Kevin G. Peters, Jing Jin, Susan E. Quaggin

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAngiogenesis and VEGF in Cancer
Canadian institutionsLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalSunnybrook Health Science Centre
FundersNational Eye InstituteJapan Society for the Promotion of ScienceRobert H. Lurie Comprehensive Cancer CenterNational Cancer InstituteNational Institutes of HealthNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteMallinckrodt PharmaceuticalsNorthwestern University
KeywordsEndotheliumAngiopoietin receptorAgonistReceptorReceptor tyrosine kinaseContext (archaeology)Lymphatic EndotheliumCell biologyAngiopoietinBiologyLymphatic systemPharmacologyCancer researchSignal transductionImmunologyEndocrinologyBiochemistryVascular endothelial growth factorVEGF receptors

Abstract

fetched live from OpenAlex

The angiopoietin (ANGPT)-TIE2/TEK signaling pathway is essential for blood and lymphatic vascular homeostasis. ANGPT1 is a potent TIE2 activator, whereas ANGPT2 functions as a context-dependent agonist/antagonist. In disease, ANGPT2-mediated inhibition of TIE2 in blood vessels is linked to vascular leak, inflammation, and metastasis. Using conditional knockout studies in mice, we show TIE2 is predominantly activated by ANGPT1 in the cardiovascular system and by ANGPT2 in the lymphatic vasculature. Mechanisms underlying opposing actions of ANGPT2 in blood vs. lymphatic endothelium are poorly understood. Here we show the endothelial-specific phosphatase VEPTP (vascular endothelial protein tyrosine phosphatase) determines TIE2 response to ANGPT2. VEPTP is absent from lymphatic endothelium in mouse in vivo, permitting ANGPT2/TIE2-mediated lymphangiogenesis. Inhibition of VEPTP converts ANGPT2 into a potent TIE2 activator in blood endothelium. Our data support a model whereby VEPTP functions as a rheostat to modulate ANGPT2 ligand effect on TIE2.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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

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 head0.026
GPT teacher head0.290
Teacher spread0.264 · 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 source (direct Gemma or distilled Codex), 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

Citations132
Published2018
Admission routes2
Has abstractyes

Explore more

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