The essential tyrosine of the internalization signal in lysosomal acid phosphatase is part of a β turn

Eberle, Wolfgang; Sander, Chris; Klaus, Werner; Schmidt, Bernhard; Figura, Kurt Von; Peters, Christoph

doi:10.1016/0092-8674(91)90296-b

Cited by 163 publications

(91 citation statements)

References 31 publications

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“…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: 88%

“…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%

“…In several receptors, a tyrosine-based motif required for receptor internalization has been described (Davis et al, 1987;Chen et al, 1990;Collawn et al, 1990;Carnfield et al, 1991;Peters et al, 1990;Eberle et al, 1991 cytoplasmic tails have demonstrated a tyrosine-based motif (YQPLK) including mouse CD3-y Y137, corresponding to human CD3-y Y138, which is sufficient to induce both internalization and delivery to lysosomes of Tac (Letourneur and Klausner, 1992b and a tails that, independently of the tyrosine-based motif, was sufficient to induce both endocytosis and delivery to lysosomes of Tac (Letourneur and Klausner, 1992b). The critical residues in the di-leucine-based motif included L130 and L131 in the mouse CD3'y tail, corresponding to L131 and L132 in the human CD3'y tail.…”

Section: Jgn-wt Cellsmentioning

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: 88%

Section: Discussionmentioning

confidence: 99%

Section: Jgn-wt Cellsmentioning

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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“…After synthesis, integral membrane proteins of lysosomes reach their destination either by an indirect route that involves trafficking to the plasma membrane, endocytosis and migration to the lysosomes, or directly from the trans-Golgi network. Tyrosine-containing motifs in the C-terminal tails are critical for lysosomal targeting of lysosome-associated membrane proteins I and II and of lysosomal acid phosphatase [208][209][210]. Deletion or mutation of the critical tyrosine results in accumulation of lysosomal acid phosphatase in the plasma membrane [208] and blocks delivery of lysosome-associated membrane protein I to the lysosome by the direct intracellular route [211].…”

Section: Lysosomal Targetingmentioning

confidence: 99%

“…Tyrosine-containing motifs in the C-terminal tails are critical for lysosomal targeting of lysosome-associated membrane proteins I and II and of lysosomal acid phosphatase [208][209][210]. Deletion or mutation of the critical tyrosine results in accumulation of lysosomal acid phosphatase in the plasma membrane [208] and blocks delivery of lysosome-associated membrane protein I to the lysosome by the direct intracellular route [211]. This suggests that similar signals are recognized by sorting proteins in the plasma membrane and the trans-Golgi network.…”

Section: Lysosomal Targetingmentioning

confidence: 99%

Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

Böhm

Grady

Bunnett

1997

Biochemical Journal

477

322

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The large and functionally diverse group of G-protein-coupled receptors includes receptors for many different signalling molecules, including peptide and non-peptide hormones and neurotransmitters, chemokines, prostanoids and proteinases. Their principal function is to transmit information about the extracellular environment to the interior of the cell by interacting with the heterotrimeric G-proteins, and they thereby participate in many aspects of regulation. Cellular responses to agonists of these receptors are usually rapidly attenuated. Mechanisms of signal attenuation include removal of agonists from the extracellular fluid, receptor desensitization, endocytosis and downregulation. Agonists are removed by dilution, uptake by transporters and enzymic degradation. Receptor desensitization is mediated by receptor phosphorylation by G-protein receptor kinases and second-messenger kinases, interaction of phosphorylated receptors with arrestins and receptor uncoupling from

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NMR conformational studies on a synthetic peptide reproducing the [1-20] processing domain of the pro-ocytocin-neurophysin precursor

et al. 1998

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The essential tyrosine of the internalization signal in lysosomal acid phosphatase is part of a β turn

Cited by 163 publications

References 31 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.

Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

NMR conformational studies on a synthetic peptide reproducing the [1-20] processing domain of the pro-ocytocin-neurophysin precursor

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