Dual Role of a Dileucine Motif in Insulin Receptor Endocytosis
Open accessAbstract
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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The conserved dileucine motif, when present on other receptors, has been shown to mediate endocytosis.
“which when present on other receptors has been shown to mediate endocytosis (Hamer et al., 1997; Haft et al., 1994).”
From LRAD3, A Novel Low-Density Lipoprotein Receptor Family Member That Modulates Amyloid Precursor Protein Trafficking (2011) · cites this paper as Hamer et al., 1997
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Collawn, J. F., Stangel, M., Kuhn, L. A., Esekogwu, V., Jing, S., Trowbridge, I. S., & Tainer, J. A. (1990) · Cell · doi:10.1016/0092-8674(90)90509-d · Cited by 518 · see citing works
Dittrich, E., Haft, C. R., Muys, L., Heinrich, P. C., & Graeve, L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.10.5487 · Cited by 160 · see citing works
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Tailor, C. S., Willett, B. J., & Kabat, D. (1999) · Journal of Virology · doi:10.1128/jvi.73.8.6500-6505.1999 · Cited by 137 · see citing works
Ranganathan, S., Noyes, N. C., Migliorini, M., Winkles, J. A., Battey, F. D., Hyman, B. T., Smith, E., Yepes, M., Mikhailenko, I., & Strickland, D. K. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5065-10.2011 · Cited by 49 · see citing works
“…consists of 151 aa, and, unlike most other members of the LDL receptor family, LRAD3 does not contain NPXY internalization sequences but instead contains a conserved dileucine motif that, when present on other receptors, has been shown to mediate endocytosis (Haft et al., 1994; Hamer et al., 1997).”
Background
- 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
- hybrid
- doi.org
- Licence
- 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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