CoChat
Sign Up
Cited by 208Autophagy in Disease and TherapyPI3K/AKT/mTOR signaling in cancerMuscle metabolism and nutrition

The DOI matches its Crossref record; 56 of the 57 references it cites were found in a registry or an index.

Amino Acids and Insulin Control Autophagic Proteolysis through Different Signaling Pathways in Relation to mTOR in Isolated Rat Hepatocytes

Open access
Kanazawa, Takumi, Taneike, Ikue, Akaishi, Ryuichiro, Yoshizawa, Fumiaki, Furuya, Norihiko, Fujimura, Shinobu, Kadowaki, Motoni·2004·Journal of Biological Chemistry
DOI 10.1074/jbc.m306337200
Open this paper in CoChat — free account

Abstract

Autophagy, a major bulk proteolytic pathway, contributes to intracellular protein turnover, together with protein synthesis. Both are subject to dynamic control by amino acids and insulin. The mechanisms of signaling and cross-talk of their physiological anabolic effects remain elusive. Recent studies established that amino acids and insulin induce p70 S6 kinase (p70(S6k)) phosphorylation by mTOR, involved in translational control of protein synthesis. Here, the signaling mechanisms of amino acids and insulin in macroautophagy in relation to mTOR were investigated. In isolated rat hepatocytes, both regulatory amino acids (RegAA) and insulin coordinately activated p70(S6k) phosphorylation, which was completely blocked by rapamycin, an mTOR inhibitor. However, rapamycin blocked proteolytic suppression by insulin, but did not block inhibition by RegAA. These contrasting results suggest that insulin controls autophagy through the mTOR pathway, but amino acids do not. Furthermore, micropermeabilization with Saccharomyces aureus alpha-toxin completely deprived hepatocytes of proteolytic responsiveness to RegAA and insulin, but still maintained p70(S6k) phosphorylation by RegAA. In contrast, Leu(8)-MAP, a non-transportable leucine analogue, did not mimic the effect of leucine on p70(S6k) phosphorylation, but maintained the activity on proteolysis. Finally, BCH, a System L-specific amino acid, did not affect proteolytic suppression or mTOR activation by leucine. All the results indicate that mTOR is not common to the signaling mechanisms of amino acids and insulin in autophagy, and that the amino acid signaling starts extracellularly with their "receptor(s)," probably other than transporters, and is mediated through a novel route distinct from the mTOR pathway employed by insulin.

Overview

Integrity signals

Registry

Crossref · 10.1074/jbc.m306337200

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Research works printed but not linked: 5

  1. Fafournoux, 2000, Biochem. J., 351, 1, 10.1042/bj3510001 · DOI
  2. van Sluijters, 2000, Biochem. J., 351, 545, 10.1042/bj3510545 · DOI
  3. Seglen, 1976, 13, 29
  4. Pacitti, 1993, Am. J. Physiol., 265, G90
  5. Shah, 2000, Am. J. Physiol., 279, E74

Cited by

Sorted by citations

See all 208

Related

See all

Metadata

Authors
Kanazawa, T., Taneike, I., Akaishi, R., Yoshizawa, F., Furuya, N., Fujimura, S., & Kadowaki, M.
Affiliations
  • Niigata University (JP)
  • Utsunomiya University (JP)
Corresponding author
Kadowaki, Motoni
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2004-02
Volume
279
Issue
9
Pages
8452-8459
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m306337200
OpenAlex
W2054125361
Cited by
208
References
57
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 13 · 2018: 5 · 2017: 10 · 2016: 7 · 2015: 8 · 2014: 16 · 2013: 12 · 2012: 9
FWCI
12.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
Keywords
autophagy, amino acids, insulin, mTOR, p70 S6 kinase, hepatocytes, leucine, rapamycin, protein turnover, amino acid signaling, alpha-toxin, BCH
MeSH terms
Amino Acids, Amino Acids, Cyclic, Animals, Bacterial Toxins, Cell Membrane, Enzyme Inhibitors, Hemolysin Proteins, Insulin, Leucine, Male, Peptide Hydrolases, Phosphorylation, Protein Kinases, Signal Transduction, Rats, Wistar, Sirolimus, Hepatocytes, Ribosomal Protein S6 Kinases, 70-kDa, Protein Kinase Inhibitors, Rats, TOR Serine-Threonine Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review