ArticleThe EMBO journal1995
Point mutations within a dimer interface homology domain of c-Mpl induce constitutive receptor activity and tumorigenicity.
Article in The EMBO journal, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 151 citations in OpenAlex.
- The thrombopoietin receptor: revisiting the master regulator of platelet production.Platelets · 2021Review
- Homomultimerization of mutant calreticulin is a prerequisite for MPL binding and activation.Leukemia · 2019Article
- Inhibition of Thrombopoietin/Mpl Signaling in Adult Hematopoiesis Identifies New Candidates for Hematopoietic Stem Cell Maintenance.PloS one · 2015Article
- Phosphorylated c-Mpl tyrosine 591 regulates thrombopoietin-induced signaling.Experimental hematology · 2014Article
- JAK/STAT signaling in hematological malignancies.Oncogene · 2013Review
- Orientation-specific signalling by thrombopoietin receptor dimers.The EMBO journal · 2011Article
- Mouse models of diseases of megakaryocyte and platelet homeostasis.Mammalian genome : official journal of the International Mammalian Genome Society · 2011Review
- Identification of the residues in the extracellular domain of thrombopoietin receptor involved in the binding of thrombopoietin and a nuclear distribution protein (human NUDC).The Journal of biological chemistry · 2010Article
- Ligand-independent thrombopoietin mutant receptor requires cell surface localization for endogenous activity.The Journal of biological chemistry · 2009Article
- New advances in the treatment of adult chronic immune thrombocytopenic purpura: role of thrombopoietin receptor-stimulating agents.Biologics : targets & therapy · 2009Article
- Article
- New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition.Leukemia · 2008Article
- Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia.Blood · 2007Article
- Agm1/Pgm3-mediated sugar nucleotide synthesis is essential for hematopoiesis and development.Molecular and cellular biology · 2007Article
- New thrombopoietic growth factors.Blood · 2007Review
- Article
- Development of hydrocephalus in mice lacking SOCS7.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- SOCS5 is expressed in primary B and T lymphoid cells but is dispensable for lymphocyte production and function.Molecular and cellular biology · 2004Article
- Suppressor screen in Mpl-/- mice: c-Myb mutation causes supraphysiological production of platelets in the absence of thrombopoietin signaling.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- An ethyl-nitrosourea-induced point mutation in phex causes exon skipping, x-linked hypophosphatemia, and rickets.The American journal of pathology · 2002Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
c-Mpl, a receptor for thrombopoietin (TPO), belongs to the haemopoietin/cytokine receptor superfamily, a group of cell surface molecules characterized by conserved sequence motifs within their ligand binding domains. A recurring mechanism for the activation of haemopoietin receptors is the formation of functional complexes by receptor subunit oligomerization. Within the growth hormone receptor, a cluster of extracellular amino acids forms a dimer interface domain that stabilizes ligand-induced homodimers. This domain appears to be functionally conserved in the erythropoietin (EPO) receptor because substitution of cysteines for residues in the analogous region causes EPO-independent receptor activation via disulfide-linked homodimerization. This report identifies an homologous domain within the c-Mpl receptor. The substitution of cysteine residues for specific amino acids in the dimer interface homology regions of c-Mpl induced constitutive receptor activity. Factor-dependent FDC-P1 and Ba/F3 cells expressing the active receptor mutants no longer required exogenous factors and proliferated autonomously. The results imply that the normal process of TPO-stimulated Mpl activation occurs through receptor homodimerization and is mediated by a conserved haemopoietin receptor dimer interface domain. Moreover, cells expressing activated mutant Mpl receptors were tumorigenic in transplanted mice. Thus, like v-mpl, its viral counterpart, mutated forms of the cellular mpl gene also have oncogenic potential.
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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.