Identification of a Leu-Ile internalization motif within the cytoplasmic domain of the leukaemia inhibitory factor receptor

Thiel, Stefan; BEHRMANN, Iris; Timmermann, Andreas; Dahmen, Heike; Müller‐Newen, Gerhard; Schaper, Fred; Tavernier, Jan; PITARD, Vincent; Heinrich, Peter C.; Graeve, Lutz

doi:10.1042/0264-6021:3390015

Cited by 14 publications

(14 citation statements)

References 7 publications

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“…Two of these sequences, lifr.a and lifr.b, are grouped with LIFR on the basis of phylogenic analysis of the CHD. One, lifr.a, showed extensive conservation of intracellular homology motifs with LIFR, including Box 1, Box 2, Box 3, multiple Stat3 binding sites and a C-terminal GSPXIXSXQFLIP internalization motif, absent in drlifr.b and OSMR [18] (Figure 5b). Although the intracellular region of drosmr was unable to be determined, the extracellular region showed strong sequence and synteny conservation with OSMR (Additional file 3).…”

Section: Resultsmentioning

confidence: 99%

Evolution of Class I cytokine receptors

2007

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Section: Resultsmentioning

confidence: 99%

Evolution of Class I cytokine receptors

2007

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“…Dileucine motifs in a number of cell surface proteins have been reported to mediate their internalization and sorting in the trans-Golgi apparatus as well as trafficking to the lysosome [24], [26]. Leucine-based internalization motifs have been identified in the mannose 6-phosphate/Insulin –like growth factor receptor, insulin receptor, CD3γ chain, epidermal growth factor receptor, leukemia inhibitory factor receptor, and gp130 subunit of the IL-6 receptor complex [7], [9], [20], [23], [25], [26], [34], [35]. In the gp130 subunit, substitution of the leucine residues in the dileucine STQPLL motif with alanines was shown to dramatically alter trafficking of the IL-6 receptor complex with a near complete loss in the capacity to internalize the receptor complex [20].…”

Section: Discussionmentioning

confidence: 99%

Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML

et al. 2008

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BackgroundExpression of truncated G-CSFR forms in patients with SCN/AML induces hyperproliferation and prolonged cell survival. Previously, we showed that ligand internalization is delayed and degradation of truncated G-CSFR forms is defective in patients with SCN/AML.Methodology/Principal FindingsIn this study, we investigated the potential roles of dileucine and tyrosine-based motifs within the cytoplasmic domain of the G-CSFR in modulating ligand/receptor internalization. Using standard binding assays with radiolabeled ligand and COS-7 cells, substitutions in the dileucine motif or deletion of tyrosine residues in the G-CSFR did not alter internalization. Attachment of the transferrin receptor YTRF internalization motif to a truncated G-CSFR form from a patient with SCN/AML corrected defective internalization, but not receptor degradation suggesting that receptor internalization and degradation occur independently via distinct domains and/or processes.ConclusionsOur data suggest that distinct domains within the G-CSFR mediate separate processes for receptor internalization and degradation. Our findings using standard binding assays differ from recently published data utilizing flow cytometry.

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“…For instance, the β chain of the IL‐2R is efficiently internalized (Hémar et al ., 1994; Subtil et al ., 1997; Lamaze et al ., 2001). Similarly, in the absence of signaling, efficient internalization of gp130 and LIF‐R occurs (Thiel et al ., 1998, 1999). The IFN‐γ R2 appears to recycle between intracellular stores and the cell surface in T lymphocytes (Rigamonti et al ., 2000).…”

Section: Discussionmentioning

confidence: 99%

The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression

2003

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The four mammalian Jak tyrosine kinases are non-covalently associated with cell surface receptors binding helical bundled cytokines. In the type I interferon receptor, Tyk2 associates with the IFNAR1 receptor subunit and positively in¯uences ligand binding to the receptor complex. Here, we report that Tyk2 is essential for stable cell surface expression of IFNAR1. In the absence of Tyk2, mature IFNAR1 is weakly expressed on the cell surface. Rather, it is localized into a perinuclear endosomal compartment which overlaps with that of recycling transferrin receptors and with early endosomal antigen-1 (EEA1) positive vesicles. Conversely, co-expressed Tyk2 greatly enhances surface IFNAR1 expression. Importantly, we demonstrate that Tyk2 slows down IFNAR1 degradation and that this is due, at least in part, to inhibition of IFNAR1 endocytosis. In addition, Tyk2 induces plasma membrane relocalization of the R2 subunit of the interleukin-10 receptor. These results reveal a novel function of a Jak protein on internalization of a correctly processed cytokine receptor. This function is distinct from the previously reported effect of other Jak proteins on receptor exit from the endoplasmic reticulum.

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Identification of a Leu-Ile internalization motif within the cytoplasmic domain of the leukaemia inhibitory factor receptor

Cited by 14 publications

References 7 publications

Evolution of Class I cytokine receptors

Evolution of Class I cytokine receptors

Divergent Pathways in COS-7 Cells Mediate Defective Internalization and Intracellular Routing of Truncated G-CSFR Forms in SCN/AML

The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression

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