ARNO but not cytohesin-1 translocation is phosphatidylinositol 3-kinase-dependent in HL-60 cells
Bibliographic record
Abstract
Cytohesin-1 and ARNO are guanine nucleotide-exchange factors (GEFs) for ADP-ribosylation factor (Arf). Here, we show that ARNO is expressed in HL-60 cells and established that granulocytic differentiation induced with Me2SO stimulated cytohesin-1 but not ARNO expression. Cytohesin-1 levels in HL-60 granulocytes were similar to those in human neutrophils. Me2SO-differentiated HL-60 cells expressed ARNO and cytohesin-1 isoforms with a diglycine and a triglycine motif in their PH domains, respectively. In vitro, ARNO diglycine and cytohesin-1 triglycine enhanced phospholipase D1 (PLD1) activation by Arf1 with near-maximal effects at 250 nM. These effects were marked particularly at low Mg2+ concentrations. PLD activation was well-correlated with GTP binding to Arf1, and cytohesin-1 was always more potent than ARNO in the PLD- and GTP-binding assays. Increasing Mg2+ concentrations reduced PLD and Arf1 activation by Arf-GEFs. fMetLeuPhe and phorbol 12-myristate 13-acetate stimulated ARNO and cytohesin-1 as well as Arf1 translocation to HL-60 cell membranes. fMetLeuPhe-mediated ARNO recruitment, but not cytohesin-1 and Arf1 translocation, was blocked by phosphatidylinositol 3-kinase inhibitors. The combined results demonstrate that cytohesin-1 triglycine participates in a major phosphatidylinositol 3-kinase-independent pathway linking cell-surface receptors to Arf1 activation and translocation in human granulocytes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".