Discovery of TBC1D1 as an Insulin-, AICAR-, and Contraction-stimulated Signaling Nexus in Mouse Skeletal Muscle
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Bibliographic record
Abstract
The Akt substrate of 160 kDa (AS160) is phosphorylated on Akt substrate (PAS) motifs in response to insulin and contraction in skeletal muscle, regulating glucose uptake. Here we discovered a dissociation between AS160 protein expression and apparent AS160 PAS phosphorylation among soleus, tibialis anterior, and extensor digitorum longus muscles. Immunodepletion of AS160 in tibialis anterior muscle lysates resulted in minimal depletion of the PAS band 160 the of PAS and we protein the AS160 regulating in expression in skeletal and the protein the 160 kDa in tibialis anterior and extensor digitorum longus muscles. and the protein PAS on skeletal muscle, we phosphorylation on and the of phosphorylation of Akt and phosphorylated in and is a PAS protein in skeletal muscle is phosphorylated in and Akt and the The Akt substrate of 160 kDa (AS160) is phosphorylated on Akt substrate (PAS) motifs in response to insulin and contraction in skeletal muscle, regulating glucose uptake. Here we discovered a dissociation between AS160 protein expression and apparent AS160 PAS phosphorylation among soleus, tibialis anterior, and extensor digitorum longus muscles. Immunodepletion of AS160 in tibialis anterior muscle lysates resulted in minimal depletion of the PAS band 160 the of PAS and we protein the AS160 regulating in expression in skeletal and the protein the 160 kDa in tibialis anterior and extensor digitorum longus muscles. and the protein PAS on skeletal muscle, we phosphorylation on and the of phosphorylation of Akt and phosphorylated in and is a PAS protein in skeletal muscle is phosphorylated in and Akt and the of is glucose in skeletal muscle is the in the and is the of glucose of glucose to the and to insulin to in glucose and glucose muscle is contraction of insulin glucose is in the muscle of the of of the insulin and and glucose of the Akt substrate of 160 kDa (AS160) substrate of 160 protein a of digitorum substrate of 160 protein a of digitorum a of and glucose a is a protein and is to in of AS160 Akt substrate motifs is to AS160 dissociation of AS160 to to of to phosphorylation of AS160 on Akt substrate motifs and glucose is a the AS160 the of AS160 phosphorylation is of of AS160 is and skeletal muscle, the protein and contraction AS160 phosphorylation glucose in skeletal muscle, AS160 phosphorylation is AS160 phosphorylation is and AS160 phosphorylation is Akt of AS160 lysates a (PAS) to phosphorylated Akt substrate motifs AS160 discovered the PAS to phosphorylated Akt substrate motifs the expression of Akt and Akt AS160 a 160 the PAS the we a dissociation between AS160 expression and apparent and AS160 phosphorylation among skeletal of the of and protein we discovered protein to AS160 and in to in is in skeletal muscle in skeletal muscle, and contraction the of phosphorylation on skeletal muscle and insulin and and the and of the on in a and a and the of and insulin and of a insulin of insulin between and in of and a and and in of to to a and the a of in the and the of the the the a of the of the of and tibialis anterior and in of to lysates of and and and a in protein the and on and and the a tibialis anterior muscle and the and and and the and of the the the in the the of the to and a the of AS160 The of AS160 the of of protein to and and of a protein to the of protein protein and to a of and of and muscle tibialis anterior muscle and extensor digitorum longus muscle lysates of of and in a of and the of the the of the of to the of of and on a a of muscle and and to the to on and the in the of the AS160 and AS160 and and the of AS160 and and the AS160 and AS160 and and of a tibialis anterior muscle The and and and of Akt of Akt and Akt in and and in and to and a of and phosphorylation the PAS AS160 and tibialis anterior muscle lysates to and and the AS160 the and AS160 the PAS and and in the and phosphorylation of AS160 the AS160 phosphorylated the PAS and and and in the the and of and the of to AS160 in to and to AS160 in of between of the The between a to we AS160 and expression in of to the of of AS160 expression expression and in soleus, and AS160 expression in muscle tibialis anterior and expression in and tibialis anterior muscles. soleus, tibialis anterior muscle, and a in tibialis anterior muscle and AS160 expression and expression of AS160 Akt substrate motifs in a PAS the PAS phosphorylated the band the PAS a of 160 to AS160 phosphorylation and glucose the of AS160 on the phosphorylation to AS160 and tibialis anterior the and of we to the of and Akt phosphorylation insulin glucose the and to the of to and Akt phosphorylation in and tibialis anterior muscle lysates the we phosphorylation among soleus, tibialis anterior, and phosphorylation in tibialis anterior muscle, AS160 expression and phosphorylation Akt phosphorylation in and tibialis anterior the in phosphorylation to to in Akt phosphorylation is in The of Akt substrate phosphorylation a of 160 and Akt phosphorylation in insulin and in and tibialis anterior muscle lysates a and phosphorylation between soleus, and lysates the AS160 is in The the a and the a muscle a on phosphorylation of the phosphorylation the of PAS phosphorylation and and phosphorylation in and tibialis anterior lysates the we phosphorylation in tibialis anterior muscle muscle phosphorylation in tibialis anterior muscle, the of phosphorylation in to of AS160 expression and phosphorylation insulin and phosphorylation is in The of Akt substrate phosphorylation a of 160 and phosphorylation in and in and tibialis anterior muscle lysates a and phosphorylation between soleus, and muscle lysates the AS160 is in The the the a muscle a on phosphorylation of in of AS160 expression and phosphorylation between and tibialis anterior the phosphorylation in tibialis anterior muscle a protein AS160 PAS phosphorylation in a of AS160 we AS160 and tibialis anterior muscle lysates and and of AS160 and muscle, the in the and in tibialis anterior muscle, AS160 depletion in AS160 a of in tibialis anterior of in to AS160 the a of 160 in and tibialis anterior muscle, AS160 and tibialis anterior muscle and AS160 AS160 and AS160 and of lysates and and a of AS160 to AS160 and and in tibialis anterior to the of in tibialis anterior muscle, lysates of the PAS to the AS160 and to and The AS160 and the and The of AS160 and the of in tibialis anterior muscle, lysates of the PAS to the AS160 and PAS to and the the protein the PAS AS160 and we the of AS160 and discovered the of the PAS protein to of we expression of in to and AS160 in and tibialis anterior AS160 expression in muscle in tibialis anterior muscle and AS160 a and the expression of the and and AS160 in soleus, tibialis anterior, and we and AS160 and The of in skeletal muscle, and in to the of AS160 in skeletal in to the of and AS160 expression and of and AS160 and muscle, to and The the a expression of and AS160 muscle, tibialis anterior muscle, and to and AS160 and of to protein expression protein expression in soleus, tibialis anterior, and protein expression in tibialis anterior muscle and AS160 to and the of and AS160 to the in soleus, tibialis anterior, and we muscle lysates of AS160 and of AS160 in to lysates Immunodepletion of tibialis anterior and muscle, resulted in muscle, of resulted in AS160 in and in tibialis the of phosphorylation in and and tibialis anterior and muscle the of AS160 and PAS is the in skeletal protein in soleus, and muscle a The a AS160 and soleus, and muscle lysates and and substrate a of 160 and AS160 protein expression in muscle muscle muscle muscle and muscle to the a tibialis anterior muscle and the and and and AS160 and the and of the the the in the tibialis anterior and muscle we and AS160 protein among and and AS160 among the of AS160 expression among soleus, and and in and in expression in muscle, in and and in muscle, expression in tibialis anterior and muscle the of among and is a in skeletal muscle, and the a in skeletal muscle, regulating of glucose the and the glucose in muscle we and tibialis anterior muscle and the PAS PAS The PAS phosphorylation insulin and to the of and and a band on a in and contraction phosphorylation and contraction phosphorylation in skeletal and tibialis anterior muscle lysates and and PAS phosphorylation to The the a in phosphorylation phosphorylated in and Akt and Akt and and Akt and muscle contraction and and Akt and in Akt and Akt resulted in in PAS phosphorylation between and PAS phosphorylation phosphorylation a in to and contraction in in and in and to phosphorylation in skeletal muscle and the and insulin in phosphorylation of and tibialis anterior muscle lysates of AS160 the PAS to phosphorylated phosphorylation between and phosphorylation and phosphorylation and tibialis anterior muscle lysates of the the PAS and phosphorylation the a of The of insulin the phosphorylation of and phosphorylation of phosphorylation and phosphorylation of between and phosphorylation to phosphorylated of the PAS the to of the the PAS of of in a The of to the of and insulin on phosphorylation and and the phosphorylation of a between the of the of to of 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phosphorylation on skeletal muscle of is glucose in skeletal muscle is the in the and is the of glucose of glucose to the and to insulin to in glucose and glucose muscle is contraction of insulin glucose is in the muscle of the of of the insulin and and glucose of the Akt substrate of 160 kDa (AS160) substrate of 160 protein a of digitorum substrate of 160 protein a of digitorum a of and glucose a Akt substrate of 160 kDa protein protein substrate a of 160 tibialis anterior extensor digitorum Akt substrate of 160 kDa protein protein substrate a of 160 tibialis anterior extensor digitorum AS160 is a protein and is to in of AS160 Akt substrate motifs is to AS160 dissociation of AS160 to to of to phosphorylation of AS160 on Akt substrate motifs and glucose is a the AS160 the of AS160 phosphorylation is of of AS160 is and skeletal muscle, the protein and contraction AS160 phosphorylation glucose in skeletal muscle, AS160 phosphorylation is AS160 phosphorylation is and AS160 phosphorylation 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of the muscle is the is the in and expression in muscle, protein a of expression in soleus, tibialis anterior, and muscle in skeletal muscle and in PAS phosphorylation of The of phosphorylation in (AS160) and tibialis anterior phosphorylation in muscle in tibialis anterior a in PAS phosphorylation of PAS to of and AS160 phosphorylation and expression in a of a to in the to of in insulin PAS phosphorylation of of to PAS phosphorylation a in PAS phosphorylation of the of of is phosphorylation The phosphorylation of and is phosphorylation and the phosphorylation and and is a the of the the PAS phosphorylated in is a phosphorylation of Akt a the of phosphorylation of The of a is in the the phosphorylation and the of the in in a of AS160 on the of and in the of the on the of the minimal of in to of in we phosphorylation of AS160 skeletal muscle glucose the tibialis anterior of and of the expression of in tibialis anterior muscle, of phosphorylation to the of phosphorylation on skeletal muscle of the of to of glucose in and glucose in skeletal muscle, we to glucose in skeletal of the expression of in muscle is a in glucose in skeletal muscle is in skeletal muscle glucose and we expression is in skeletal muscle, and contraction and Akt and in we phosphorylation of insulin and phosphorylation of is the of of phosphorylation on skeletal muscle is a of the and AS160 and AS160 and a a and a The and AS160 between and AS160 is the of Akt substrate motifs AS160 Akt substrate and insulin phosphorylation of is in The is phosphorylation of AS160 Akt substrate motifs and glucose the of is is the substrate a of 160 in tibialis anterior and to the tibialis anterior and muscle, the of and AS160 in the and to of the muscle is the is the in and expression in muscle, protein a of expression in soleus, tibialis anterior, and muscle in skeletal muscle and in PAS phosphorylation of The of phosphorylation in (AS160) and tibialis anterior phosphorylation in muscle in tibialis anterior a in PAS phosphorylation of PAS to of and AS160 phosphorylation and expression in muscles. a of a to in the to of in insulin PAS phosphorylation of of to PAS phosphorylation a in PAS phosphorylation of the of of is phosphorylation The phosphorylation of and is phosphorylation and the phosphorylation and and is a the of the the PAS phosphorylated in is a phosphorylation of Akt a the of phosphorylation The of The of a is in the the phosphorylation and the of the in in a of AS160 on the of and in the of the on the of the minimal of in to of in we phosphorylation of AS160 skeletal muscle glucose the tibialis anterior of and of the expression of in tibialis anterior muscle, of phosphorylation to the of phosphorylation on skeletal muscle of the of to of glucose in and glucose in skeletal muscle, we to glucose in skeletal of the expression of in muscle is a in glucose in skeletal muscle is in skeletal muscle glucose and we expression is in skeletal muscle, and contraction and Akt and in we phosphorylation of insulin and phosphorylation of is the of of phosphorylation on skeletal muscle and the and and the of AS160 and
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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