Cited by 59Cellular transport and secretionMetabolism, Diabetes, and CancerReceptor Mechanisms and Signaling

Dual Role of a Dileucine Motif in Insulin Receptor Endocytosis

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Hamer, Isabelle, Haft, Carol Renfrew, Paccaud, Jean-Pierre, Maeder, Christine, Taylor, Simeon, Carpentier, Jean-Louis·1997·Journal of Biological Chemistry

Abstract

Two leucines (Leu986 and Leu987) have recently been shown to take part in the control of human insulin receptor (HIR) internalization (Renfrew-Haft, C., Klausner, R. D., and Taylor, S. I. (1994) J. Biol. Chem. 269, 26286-26294). The aim of the present study was to further investigate the exact mechanism of this control process. Constitutive and insulin-induced HIR internalizations were studied biochemically and morphologically in NIH 3T3 cells overexpressing either a double alanine (amino acid residues 986-987) mutant HIR (HIR AA1) or HIR truncated at either amino acid residue 981 (HIR Delta981) or 1000 (HIR Delta1000). Data collected indicate that: (a) the three mutant HIR show a reduced association with microvilli as compared with HIR wild-type; (b) the two receptors containing the dileucine motif (HIR WT and HIR Delta1000) show the highest propensity to associate with clathrin-coated pits, independently of kinase activation; (c) the two receptors lacking the dileucine motif but containing two tyrosine-based motifs, previously described as participating in clathrin-coated pit segregation, associate with these surface domains with a lower affinity than the two others, (d) in the presence of the kinase domain, an unmasking of the tyrosine-based motifs mediated by kinase activation is required. These results indicate that the dileucine motif is not sufficient by itself, but participates in anchoring HIR on microvilli and that another sequence, located downstream from position…

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Crossref · 10.1074/jbc.272.35.21685

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Authors
Hamer, I., Haft, C. R., Paccaud, J.-P., Maeder, C., Taylor, S., & Carpentier, J.-L.
Affiliations
University of Geneva (CH)
Corresponding author
Carpentier, Jean-Louis
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1997-08
Volume
272
Issue
35
Pages
21685-21691
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1985621508
Cited by
59
References
2
Citations by year
2025: 1 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 2 · 2014: 2 · 2013: 1 · 2012: 2
FWCI
2.84
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Repository of the University of Namur (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
insulin receptor, dileucine motif, receptor internalization, clathrin-coated pits, tyrosine-based motif, microvilli, receptor sorting, kinase activation, receptor truncation, NIH3T3 cells
MeSH terms
Animals, Coated Pits, Cell-Membrane, Endocytosis, Humans, Insulin, Leucine, Receptor, Insulin, Structure-Activity Relationship, Transfection, Mutagenesis, 3T3 Cells, Mice

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