ArticleProceedings of the National Academy of Sciences of the United States of America1997
Dissecting the thrombopoietin receptor: functional elements of the Mpl cytoplasmic domain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 154 citations in OpenAlex.
- A review on the functional characteristics of the c-Myeloproliferative Leukaemia (c-MPL) gene and its isoforms.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease.Leukemia · 2024Article
- A newly identified 45-kDa JAK2 variant with an altered kinase domain structure represents a novel mode of JAK2 kinase inhibitor resistance.Molecular oncology · 2024Article
- The thrombopoietin receptor: revisiting the master regulator of platelet production.Platelets · 2021Review
- Classical and novel GH receptor signaling pathways.Molecular and cellular endocrinology · 2020Review
- c-Mpl and TPO expression in the human central nervous system neurons inhibits neuronal apoptosis.Aging · 2020Article
- Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution.Pharmacological reviews · 2020Review
- Cytokine receptor splice variants in hematologic diseases.Cytokine · 2020Review
- Defining the requirements for the pathogenic interaction between mutant calreticulin and MPL in MPN.Blood · 2018Article
- Dissection of Signaling Events Downstream of the c-Mpl Receptor in Murine Hematopoietic Stem Cells Via Motif-Engineered Chimeric Receptors.Stem cell reviews and reports · 2018Article
- Hematopoietic Cytokine Gene Duplication in Zebrafish Erythroid and Myeloid Lineages.Frontiers in cell and developmental biology · 2018Review
- The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects.Frontiers in endocrinology · 2018Review
- Lung Endothelial MicroRNA-1 Regulates Tumor Growth and Angiogenesis.American journal of respiratory and critical care medicine · 2017Article
- From chronic immune thrombocytopenia to severe aplastic anemia: recent insights into the evolution of eltrombopag.Therapeutic advances in hematology · 2017Review
- Dual role of IL-21 in megakaryopoiesis and platelet homeostasis.Haematologica · 2017Article
- The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by Ligand, Mutations, Agonists, and Mutated Calreticulin.Frontiers in endocrinology · 2017Review
- Article
- Inefficient megakaryopoiesis in mouse hematopoietic stem-progenitor cells lacking T-bet.Experimental hematology · 2016Article
- A Novel Peptide Thrombopoietin Mimetic Designing and Optimization Using Computational Approach.Frontiers in bioengineering and biotechnology · 2016Article
- Tyrosine 625 plays a key role and cooperates with tyrosine 630 in MPL W515L-induced signaling and myeloproliferative neoplasms.Cell & bioscience · 2016Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Thrombopoietin (TPO) acts through its receptor, Mpl, to stimulate the proliferation and maturation of megakaryocytes and their progenitors. The Mpl cytoplasmic domain controls this process through assembly of an active signaling complex using various receptor docking sites. In this report, eight carboxyl truncations of the 121-aa murine Mpl cytoplasmic domain were tested for the ability to support growth of a cytokine-dependent cell line (Ba/F3) and for their capacity to induce TPO-stimulated tyrosine phosphorylation of specific signaling proteins. Point mutations of the five tyrosine residues in the cytoplasmic domain of the receptor were subsequently used to confirm our conclusions. From these studies we demonstrate that: (i) TPO-induced proliferation is moderately reduced by truncation of as many as 53 C-terminal amino acids of Mpl, including the sites of receptor tyrosine phosphorylation; (ii) truncation/mutation of residues 69-83 of the Mpl cytoplasmic domain enhances proliferative signaling, perhaps mediated by a decrease in receptor-driven cellular differentiation; (iii) Mpl can be phosphorylated at either Y112 or Y117 but not at the three proximal cytoplasmic tyrosine residues (Y8, Y29, and Y78); (iv) Y112 of Mpl is necessary for tyrosine phosphorylation of Shc and Shc-associated p145 (SHIP); and (v) unlike STAT3, STAT5 is partially phosphorylated in the absence of any tyrosine residues in the Mpl cytoplasmic domain. These studies identify subdomains of Mpl necessary for activation of several critical signaling pathways and point to two potentially novel mechanisms of TPO-induced signal transduction, an indirect pathway to STAT5 activation and a differentiation domain that acts by limiting proliferation.
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