ArticleThe Journal of biological chemistry2012
Large putative PEST-like sequence motif at the carboxyl tail of human calcium receptor directs lysosomal degradation and regulates cell surface receptor level.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Biology of PEST-containing nuclear proteins as potential targets in ovarian cancer (Review).Oncology letters · 2026Review
- The role and potential mechanism of PEST-containing nuclear protein (PCNP) in endothelial cell angiogenesis in vitro.Scientific reports · 2025Article
- A calcium-sensing receptor dileucine motif directs internalization to spatially distinct endosomal signaling pathways.iScience · 2025Article
- Molecular regulation of calcium-sensing receptor (CaSR)-mediated signaling.Chronic diseases and translational medicine · 2024Review
- PRP4 Promotes Skin Cancer by Inhibiting Production of Melanin, Blocking Influx of Extracellular Calcium, and Remodeling Cell Actin Cytoskeleton.International journal of molecular sciences · 2021Article
- Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor.Science advances · 2021Article
- Calcium-sensing receptor signaling - How human disease informs biology.Current opinion in endocrine and metabolic research · 2021Article
- International Union of Basic and Clinical Pharmacology. CVIII. Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function.Pharmacological reviews · 2020Review
- A Retrospective on eIF2A-and Not the Alpha Subunit of eIF2.International journal of molecular sciences · 2020Review
- Sensory Axon Growth Requires Spatiotemporal Integration of CaSR and TrkB Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Family C G-Protein-Coupled Receptors in Alzheimer's Disease and Therapeutic Implications.Frontiers in pharmacology · 2019Review
- Identification of a PEST Sequence in Vertebrate KFrontiers in physiology · 2019Article
- The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.Nature reviews. Endocrinology · 2018Review
- The Listeriolysin O PEST-like Sequence Co-opts AP-2-Mediated Endocytosis to Prevent Plasma Membrane Damage during Listeria Infection.Cell host & microbe · 2018Article
- The GPRC6A receptor displays constitutive internalization and sorting to the slow recycling pathway.The Journal of biological chemistry · 2017Article
- Molecular Basis of the Extracellular Ligands Mediated Signaling by the Calcium Sensing Receptor.Frontiers in physiology · 2016Review
- 14-3-3 Proteins Buffer Intracellular Calcium Sensing Receptors to Constrain Signaling.PloS one · 2015Article
- A mechanism for epithelial-mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3).The Biochemical journal · 2013Article
- Minireview: the intimate link between calcium sensing receptor trafficking and signaling: implications for disorders of calcium homeostasis.Molecular endocrinology (Baltimore, Md.) · 2012Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
A deletion between amino acid residues Ser(895) and Val(1075) in the carboxyl terminus of the human calcium receptor (hCaR), which causes autosomal dominant hypocalcemia, showed enhanced signaling activity and increased cell surface expression in HEK293 cells (Lienhardt, A., Garabédian, M. G., Bai, M., Sinding, C., Zhang, Z., Lagarde, J. P., Boulesteix, J., Rigaud, M., Brown, E. M., and Kottler, M. L. (2000) J. Clin. Endocrinol. Metab. 85, 1695-1702). To identify the underlying mechanism(s) for these increases, we investigated the effects of carboxyl tail truncation and deletion in hCaR mutants using a combination of biochemical and cell imaging approaches to define motifs that participate in regulating cell surface numbers of this G protein-coupled receptor. Our data indicate a rapid constitutive receptor internalization of the cell surface hCaR, accumulating in early (Rab7 positive) and late endosomal (LAMP1 positive) sorting compartments, before targeting to lysosomes for degradation. Recycling of hCaR back to the cell surface was also evident. Truncation and deletion mapping defined a 51-amino acid sequence between residues 920 and 970 that is required for targeting to lysosomes and degradation but not for internalization or recycling of the receptor. No singular sequence motif was identified, instead the required sequence elements seem to distribute throughout this entire interval. This interval includes a high proportion of acidic and hydroxylated amino acid residues, suggesting a similarity to PEST-like degradation motif (PESTfind score of +10) and several glutamine repeats. The results define a novel large PEST-like sequence that participates in the sorting of internalized hCaR routed to the lysosomal/degradation pathway that regulates cell surface receptor numbers.
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