ArticleBlood2008
YRRL motifs in the cytoplasmic domain of the thrombopoietin receptor regulate receptor internalization and degradation.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 79 citations in OpenAlex.
- Thrombopoietin Receptor MPL in Hematopoiesis and Myeloproliferative Neoplasms: Physiological Roles and Pathogenic Mechanisms.Stem cell reviews and reports · 2026Review
- Beyond TFRC: The Pivotal Role of mGluR2 in Feline Calicivirus Entry and Replication.Veterinary sciences · 2025Article
- Lysosomal degradation targets mutant calreticulin and the thrombopoietin receptor in myeloproliferative neoplasms.Blood advances · 2024Article
- Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease.Leukemia · 2024Article
- Effects of calreticulin mutations on cell transformation and immunity.Journal of cellular and molecular medicine · 2023Review
- Inherited Thrombocytopenia Caused by Variants in Crucial Genes for Glycosylation.International journal of molecular sciences · 2023Review
- New insights of platelet endocytosis and its implication for platelet function.Frontiers in cardiovascular medicine · 2023Review
- New functions of C3G in platelet biology: Contribution to ischemia-induced angiogenesis, tumor metastasis and TPO clearance.Frontiers in cell and developmental biology · 2022Article
- Endocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice.Frontiers in oncology · 2022Article
- In and out: Traffic and dynamics of thrombopoietin receptor.Journal of cellular and molecular medicine · 2021Review
- Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications.International journal of molecular sciences · 2021Review
- The thrombopoietin receptor: revisiting the master regulator of platelet production.Platelets · 2021Review
- C-Cbl regulates c-MPL receptor trafficking and its internalization.Journal of cellular and molecular medicine · 2020Article
- Orchestration of signaling by structural disorder in class 1 cytokine receptors.Cell communication and signaling : CCS · 2020Article
- Clinical acceleration ofHaematologica · 2020Article
- Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations.Science (New York, N.Y.) · 2020Article
- Deciphering the Role of the Coagulation Cascade and Autophagy in Cancer-Related Thrombosis and Metastasis.Frontiers in oncology · 2020Review
- Platelets and Immune Responses During Thromboinflammation.Frontiers in immunology · 2019Review
- Cytokine Receptor Endocytosis: New Kinase Activity-Dependent and -Independent Roles of PI3K.Frontiers in endocrinology · 2017Review
- The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by Ligand, Mutations, Agonists, and Mutated Calreticulin.Frontiers in endocrinology · 2017Review
Corrections and comments
- Commented on by
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Thrombopoietin (Tpo), acting through the c-Mpl receptor, promotes the survival and proliferation of hematopoietic stem and progenitor cells and drives megakaryocyte differentiation. The proproliferation and survival signals activated by Tpo must therefore be tightly regulated to prevent uncontrolled cell growth. In this work, we determined the mechanisms that control Tpo-stimulated c-Mpl internalization and defined the processes leading to its degradation. Stimulation of BaF-Mpl cells with Tpo leads to rapid, clathrin-dependent endocytosis of the receptor. Using small interfering RNA (siRNA), we found that inhibition of adaptor protein 2 (AP2), which mediates endocytosis of transmembrane proteins, strongly attenuates Tpo-stimulated c-Mpl internalization. AP2 interacts with YXXPhi motifs and we identified 2 such motifs in c-Mpl (Y(8)RRL and Y(78)RRL) and investigated Tpo-stimulated internalization of receptors bearing point mutations at these sites. After Tpo stimulation, internalization was greatly reduced in c-Mpl Y(78)F and c-Mpl Y(8+78)F, and these cell lines also exhibited increased proliferation and increased strength and duration of Jak2, STAT5, AKT, and ERK1/2 activation in response to Tpo. We also found that the Y(8)RRL motif regulates Tpo-stimulated lysosomal degradation of c-Mpl. Our data establishes that c-Mpl cytoplasmic YRRL motifs are responsible for both Tpo-mediated internalization via interactions with AP2 and lysosomal targeting after endocytosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.