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Cited by 35Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase Signaling

Compartmentalization and Insulin-Induced Translocations of Insulin Receptor Substrates, Phosphatidylinositol 3-Kinase, and Protein Kinase B in Rat Liver**This work was supported by grants from the Medical Research Council and from the National Cancer Institute of Canada, and by the Cleghorn Fund at McGill University and the M. Pollack Foundation of Montreal.

Balbis, Alejandro, Baquiran, Gerry, Bergeron, John J. M., Posner, Barry I.·2000·Endocrinology
DOI 10.1210/endo.141.11.7774
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Abstract

Physiological doses of insulin in rats resulted in a rapid redistribution of key signaling proteins between subcellular compartments in rat liver. In plasma membranes (PM) and microsomes, insulin induced a rapid decrease in insulin receptor substrate-1/2 (IRS1/2) within 30 sec and an increase in these proteins in endosomes (EN) and cytosol. The level of p85 in PM increased 2.3-fold at 30 sec after insulin stimulation followed by a decrease at 2 min. In this interval, 60-85% and 10-20% of p85 in PM was associated with IRS1 and IRS2, respectively. Thus, in PM, IRS1/2 accounts for almost all of the protein involved in phosphatidylinositol 3-kinase activation. In ENs insulin induced a maximal increase of 40% in p85 recruitment. As in PM, almost all p85 was associated with IRS1/2. The greater level of p85 recruitment to PM was associated with a higher level of insulin-induced recruitment of Akt1 to this compartment (4.0-fold in PM vs. 2.4-fold in EN). There was a close correlation between Akt1 activity and Akt1 phosphorylation at Thr308 and Ser473 in PM and cytosol. However, in ENs the level of Akt1 activity per unit of phosphorylated Akt1 was significantly greater than in PM, indicating that in addition to phosphorylation, another factor(s) modulates Akt1 activation by insulin in rat liver. Our results demonstrate that activation of the insulin receptor kinase and modulation of key components of the insulin signaling cascade occur at the cell surface and within the endosomal system. These data provide further support for the role of the endocytic process in cell signaling.

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  • The endosomal system functions like a digital-analogue computer that regulates the specificity and robustness of the insulin signaling response in SkM.

    “For instance, the endosomal system functions like a digital-analogue computer that regulates the specificity and robustness of the insulin signaling response in the SkM (i.e., insulin induces translocation of key signaling proteins into endosome) (Balbis et al., 2000; Jethwa et al., 2015).”

    From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Balbis et al., 2000

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Authors
Balbis, A., Baquiran, G., Bergeron, J. J. M., & Posner, B. I.
Affiliations
McGill University (CA)
Corresponding author
Posner, Barry I.
ORCID
Bergeron, John J. M.
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2000-11-01
Volume
141
Issue
11
Pages
4041-4049
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/endo.141.11.7774
OpenAlex
W2163572207
Cited by
35
References
42
Citations by year
2025: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2016: 2 · 2015: 1 · 2014: 4 · 2012: 1
FWCI
0.84
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
insulin signaling, IRS-1, insulin receptor substrate 2, phosphatidylinositol 3-kinase, p85 regulatory subunit, AKT1, protein translocation, subcellular compartmentalization, endosomes, plasma membrane, liver, endocytosis, Akt1 phosphorylation
MeSH terms
Animals, Cell Membrane, Enzyme Activation, Female, Insulin, Kinetics, Liver, Microsomes, Liver, Phosphoproteins, Phosphorylation, Plant Proteins, Proto-Oncogene Proteins, Receptor, Insulin, Potassium Channels, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Arabidopsis Proteins, Intracellular Signaling Peptides and Proteins, Proto-Oncogene Proteins c-akt, Rats, Insulin Receptor Substrate Proteins

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