The NPXY internalization signal of the LDL receptor adopts a reverse-turn conformation

Bansal, Anu; Gierasch, Lila M.

doi:10.1016/0092-8674(91)90295-a

Cited by 243 publications

(181 citation statements)

References 32 publications

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“…The internalization sequences of both LDLR and TfR most probably adopt a tight turn conformation (Collawn et al, 1990;Ktistakis et al, 1990;Bansal and Gierasch, 1991). Similar tyrosine-based internalization motifs have been described in the mannose 6-phosphate/insulin-like growth factor-Il receptor (Man-6-P/IGF-IIR) and in lysosomal acid phosphatase (LAP) (Peters et al, 1990;Carnfield et al, 1991;Eberle et al, 1991).…”

Section: Introductionmentioning

confidence: 79%

“…Most of these motifs contain a tyrosine and some of them are predicted to adopt a tight turn conformation (Davis et al, 1987;Chen et al, 1990;Collawn et al, 1990; Ktistakis et al, 1990;Peters et al, 1990;Bansal and Gierasch, 1991;Carnfield et al, 1991;Eberle et al, 1991). Detailed which become phosphorylated and are known to be required for PKC-mediated internalization are in bold and underlined.…”

Section: Discussionmentioning

confidence: 99%

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CD3 gamma contains a phosphoserine-dependent di-leucine motif involved in down-regulation of the T cell receptor.

et al. 1994

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Several cell surface receptors including the T cell receptor (TCR) are phosphorylated and down-regulated following activation of protein kinase C (PKC). Among other substrates the activated PKC in T cells phosphorylates the CD3-y subunit of the TCR. To investigate the role of CD3'y phosphorylation in PKC-mediated TCR downregulation, point mutated CD3,y cDNA was transfected into the CD3'y-negative T cell line JGN and CD3'y transfectants were analysed. Phosphorylation at S126 but not S123 in the cytoplasmic tail of CD3-y was required for PKC-mediated down-regulation of the TCR. Furthermore, analysis of a series of CD3'y truncation mutants indicated that in addition to S126 phosphorylation a motif C-terminal of S126 was required for TCR down-regulation. Point mutation analyses confirmed this observation and demonstrated that a membrane-proximal di-leucine motif (L131 and L132) in the cytoplasmic tail of CD3'y was required for PKC-mediated TCR downregulation in addition to phosphorylation at S126. Incubation of T cells in hypertonic medium known to disrupt normal clathrin lattices severely inhibited PKCmediated TCR down-regulation in non-mutated T cells, indicating that the TCR was down-regulated by endocytosis via clathrin coated pits. Based on the present results and previously published observations on intracellular receptor sorting, a general model for intracellular sorting of receptors containing di-leucineor tyrosine-based motifs is proposed.

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Section: Introductionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

CD3 gamma contains a phosphoserine-dependent di-leucine motif involved in down-regulation of the T cell receptor.

et al. 1994

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“…Hence, we propose the LPGG tetrapeptide to be one of the features required for efficient endocytosis of the short PRLR. Proline is a strong ␤-turn promoter, especially in position 2 (6,42), which strengthens the likelihood that this motif adopts such a secondary fold in the PRLR. For some receptors, requirement of an aromatic residue within the ␤-turn has also been described.…”

Section: Discussionmentioning

confidence: 99%

“…1). Endocytotic codes have been identified as short linear arrays of amino acids which, despite their low degree of sequence similarity, are all assumed to fold in a tight ␤-turn (6,7). These motifs may be recognized specifically by plasma membrane-associated adaptor proteins, or AP-2, which mediate the recruitment of these receptors into clathrin-coated pits and promote high-efficiency endocytosis (for review, see Refs.…”

mentioning

confidence: 99%

Identification of Cytoplasmic Motifs Required for Short Prolactin Receptor Internalization

Vincent

Goffin

Rozakis-Adcock

et al. 1997

Journal of Biological Chemistry

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Cloning of rat prolactin receptor (PRLR) cDNAs revealed the existence of two isoforms, termed short and long according to the length of their cytoplasmic domain. Internalization studies show, first, that PRLR internalization is hormone-dependent and, second, that ligand-receptor complexes of the short PRLR are internalized to a larger extent compared to the long form. In order to identify regions within the cytoplasmic domain of the short PRLR required for efficient internalization, serial truncations of the cytoplasmic tail were performed by inserting a stop codon in place of those encoding residues 282, 273, 262, 253, 244, or 237 (wild type short PRLR contains 291 amino acids). Our data show that two motifs, lying within residues 253-261 and 273-281, are involved in internalization. Both regions contain a consensus feature identified within other receptors as internalization signals, namely a di-leucine peptide (amino acids 259 -260) and a tetrapeptide predicted to adopt a ␤-turn structure (amino acids 276 -279). We propose these two motifs are involved in PRLR endocytosis. Finally, we show that ␣-adaptin, a component of adaptor protein AP-2, coprecipitates with short PRLR complexes upon PRL stimulation, which strongly suggests that PRLR internalization is mediated by the clathrin-coated pits endocytotic pathway.

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“…Tyrosine-based signals have been proposed to be turn structures as well (16,(23)(24)(25), and have been shown to form independent structural motifs because one tyrosine-based signal can often substitute for another (26 -28). Whether di-leucinebased signals form independent structural motifs is unknown.…”

mentioning

confidence: 99%

Structural Requirements for Major Histocompatibility Complex Class II Invariant Chain Endocytosis and Lysosomal Targeting

Kang

Liang

Parker

et al. 1998

Journal of Biological Chemistry

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The NPXY internalization signal of the LDL receptor adopts a reverse-turn conformation

Cited by 243 publications

References 32 publications

CD3 gamma contains a phosphoserine-dependent di-leucine motif involved in down-regulation of the T cell receptor.

CD3 gamma contains a phosphoserine-dependent di-leucine motif involved in down-regulation of the T cell receptor.

Identification of Cytoplasmic Motifs Required for Short Prolactin Receptor Internalization

Structural Requirements for Major Histocompatibility Complex Class II Invariant Chain Endocytosis and Lysosomal Targeting

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