Calcium‐ and FK506‐independent interaction between the immunophilin FKBP51 and calcineurin*
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Bibliographic record
Abstract
FKBP51 is a member of the immunophilin family having intrinsic peptidyl-prolyl cis-trans-isomerase (PPIase) activity. Its enzymatic activity is inhibited by binding either immunosuppressive agent FK506 or rapamycin. Similar to FKBP12, but at higher concentrations of FK506, FKBP51 has been shown to inhibit the serine/threonine phosphatase activity of calcineurin in the presence of calcium and calmodulin. Here we show that a glutathione S-transferase (GST) fusion protein of FKBP51 on glutathione-Sepharose beads precipitated both purified calcineurin from bovine brain and calcineurin from murine T cell lysates. Surprisingly, the binding of GST-FKBP51 to calcineurin was FK506-independent and independent of a requirement for calcium or exogenous calmodulin. Unlike FKBP12, FKBP51 transiently expressed in COS-7 cells was precipitated by calcineurin bound to calmodulin-Sepharose beads in the absence of either FK506 or rapamycin. Unlike FKBP12, however, overexpression of FKBP51 in Jurkat T cells did not significantly affect the transcriptional activation of nuclear factor of activated T cells (NFAT) upon physiological stimulation, nor did it affect the ability of FK506 to inhibit NFAT-driven transcription. We generated a series of FKBP51 mutations to map the interaction of FKBP51 with calcineurin. Deletion of the aminoterminal, FKBP12-like domain of FKBP51 did not affect the ability of FKBP51 to bind to purified calcineurin, while deletion of the FKBP51 carboxyterminal domain abrogated the ability of FKBP51 to bind to calcineurin. Taken together, these results demonstrate a novel interaction between calcineurin and the immunophilin FKBP51 that is independent of calcium, calmodulin, and drug. The binding site on calcineurin for FKBP51 is separable from the immunophilin PPIase-active and drug-binding site.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it