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Leupaxin is serine phosphorylated and recruited to the immunological synapse upon TCR engagement in cytotoxic T lymphocytes (CTL)

2017· article· en· W4313356124 on OpenAlexaff
Hanne L. Ostergaard

Bibliographic record

VenueThe Journal of Immunology · 2017
Typearticle
Languageen
FieldMedicine
TopicCell Adhesion Molecules Research
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsImmunological synapsePhosphorylationT-cell receptorTyrosine phosphorylationCell biologyBiologySignal transducing adaptor proteinCytotoxic T cellSerinePaxillinTyrosineCD8IntegrinT cellReceptorBiochemistryImmune systemImmunologyFocal adhesion

Abstract

fetched live from OpenAlex

Abstract Background Leupaxin is a member of paxillin family proteins that function as adaptor proteins in integrin signaling. Compared to other members, leupaxin is mainly expressed in leukocytes. However, the role of leupaxin in T cells is unknown. Results Leupaxin has been shown to be tyrosine phosphorylated in cells including tumor cells, fibroblasts and B cells. However we detected no leupaxin tyrosine phosphorylation in T cells. Instead, leupaxin showed mobility shift in response to TCR signaling. We demonstrated that the mobility shift was caused by serine phosphorylation and was ERK dependent. Although leupaxin is downstream of integrin receptors, LFA-1 stimulation did not induce leupaxin phosphorylation. Several potentially phosphorylated residues were mutated into alanine individually. When Ser54 was mutated, leupaxin no longer showed mobility shift, suggesting that leupaxin is phosphorylated at Ser54. Leupaxin was recruited to the immunological synapse and colocalized with LFA-1. Leupaxin has N-terminal leucine-aspartic acid (LD) domains and C-terminal LIM domains that contain four double zinc finger motifs. The LIM domains were dispensable for leupaxin localization at the contact zone. Leupaxin failed to be recruited to the immunological synapse after deleting LD2–4 domains, suggesting the importance of LD2–4 domains for the recruitment. Conclusions Leupaxin is not tyrosine phosphorylated but serine phosphorylated at Ser54 in response to TCR engagement. Leupaxin is recruited to the immunological synapse through LD2–4 domains. Studies are underway to determine the contribution of leupaxin to CTL adhesion, polarization and degranulation.

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 score0.003
Threshold uncertainty score0.009

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)0.0030.001

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 head0.047
GPT teacher head0.332
Teacher spread0.285 · 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".

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Citations0
Published2017
Admission routes1
Has abstractyes

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