Cited by 1,070Metabolism, Diabetes, and CancerProtein Kinase Regulation and GTPase SignalingPancreatic function and diabetes

Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose

Ellis, Leland, Clauser, Eric, Morgan, David O., Edery, Marc, Roth, Richard A., Rutter, William J.·1986·Cell

Abstract

Insulin stimulates the autophosphorylation of tyrosine residues of the beta subunit of the insulin receptor (IR); this modified insulin-independent kinase has increased activity toward exogenous substrates in vitro. We show here that replacement of one or both of the twin tyrosines (residues 1162 and 1163) with phenylalanine results in a dramatic reduction in or loss of insulin-activated autophosphorylation and kinase activity in vitro. In vivo, these mutations not only result in a substantial decrease in insulin-stimulated IR autophosphorylation but also in a parallel decrease in the insulin-activated uptake of 2-deoxyglucose. Furthermore, a truncated IR protein (lacking the last 112 amino acids) has an unstable beta subunit; this mutant has no kinase activity in vitro or in vivo and does not mediate insulin-stimulated uptake of 2-deoxyglucose. IR autophosphorylation is thus implicated in the regulation of IR activities, with tyrosines 1162 and 1163 as major sites of this regulation.

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Crossref · 10.1016/0092-8674(86)90786-5

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54 of 54 references verified0 citation errors · 0 not checkable

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  • Mutagenesis of any of the three major phosphorylation sites (residues 1158, 1163, and 1162) impairs insulin receptor tyrosine kinase activity, decreasing metabolic and growth-promoting effects of insulin.

    “Mutagenesis of any of the three major phosphorylation sites (at residues 1158, 1163, and 1162) impairs insulin receptor tyrosine kinase activity, leading to a decrease in the metabolic and growth-promoting effects of insulin [141, 142].”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [141]

  • PI3K inhibitors impair glucose transport and block activation of glycogen synthase and HK-II expression.

    “Inhibitors of PI3K impair glucose transport and block the activation of glycogen synthase and hexokinase- (HK-) II expression [138–146]”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [141]

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Authors
Ellis, L., Clauser, E., Morgan, D. O., Edery, M., Roth, R. A., & Rutter, W. J.
Affiliations
  • University of California, San Francisco (US)
  • Stanford University (US)
Venue
Cell
Publisher
Elsevier BV
Published
1986-06
Volume
45
Issue
5
Pages
721-732
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2030156849
Cited by
1,070
References
57
Citations by year
2026: 1 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 4 · 2013: 1 · 2012: 5
FWCI
34.23
Type
journal article
Language
en
Open access
closed
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01am021344-09, 5r01am034926-02)
  • National Institute of General Medical Sciences (GM 28520)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
insulin receptor, insulin receptor beta-subunit, autophosphorylation, 2-deoxyglucose uptake, insulin signaling, point mutations
MeSH terms
Amino Acid Sequence, Animals, Cell Line, Cricetulus, Deoxy Sugars, Deoxyglucose, DNA, Female, Gene Expression Regulation, Cricetinae, Humans, Insulin, Ovary, Phosphorylation, Protein-Tyrosine Kinases, Receptor, Insulin, Transfection, Tyrosine

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