Mpl

Summary

Gene Symbol: Mpl
Description: myeloproliferative leukemia virus oncogene
Alias: CD110, TPO-R, c-mpl, hlb219, thrombopoietin receptor, myeloproliferative leukemia protein, proto-oncogene c-Mpl
Species: mouse
Products:     Mpl

Top Publications

  1. Fielder P, Gurney A, Stefanich E, Marian M, Moore M, Carver Moore K, et al. Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets. Blood. 1996;87:2154-61 pubmed
    The involvement of platelets and the c-mpl receptor in the regulation of thrombopoietin (TPO) plasma concentrations and tissue mRNA levels was investigated in both normal mice and mice defective in c-mpl (c-mpl-/-)...
  2. Carver Moore K, Broxmeyer H, Luoh S, Cooper S, Peng J, Burstein S, et al. Low levels of erythroid and myeloid progenitors in thrombopoietin-and c-mpl-deficient mice. Blood. 1996;88:803-8 pubmed
    Thrombopoietin (TPO), the ligand for the c-mpl receptor, has been shown to be the major regulator of platelet production...
  3. Dahlen D, Broudy V, Drachman J. Internalization of the thrombopoietin receptor is regulated by 2 cytoplasmic motifs. Blood. 2003;102:102-8 pubmed
    ..However, the processes that regulate Mpl internalization have not previously been described...
  4. Petit Cocault L, Volle Challier C, Fleury M, Peault B, Souyri M. Dual role of Mpl receptor during the establishment of definitive hematopoiesis. Development. 2007;134:3031-40 pubmed
    ..b>Mpl receptor and its ligand, TPO, have been shown to play an essential role in the early steps of adult hematopoiesis...
  5. Fox N, Chen R, Hitchcock I, Keates Baleeiro J, Frangoul H, Geddis A. Compound heterozygous c-Mpl mutations in a child with congenital amegakaryocytic thrombocytopenia: functional characterization and a review of the literature. Exp Hematol. 2009;37:495-503 pubmed publisher
    To genetically and functionally characterize mutations of c-Mpl that lead to thrombocytopenia in a child with congenital amegakaryocytic thrombocytopenia...
  6. Ihara K, Ishii E, Eguchi M, Takada H, Suminoe A, Good R, et al. Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia. Proc Natl Acad Sci U S A. 1999;96:3132-6 pubmed
    ..Our previous hematological analysis indicated similarities between human CAMT and murine c-mpl (thrombopoietin receptor) deficiency...
  7. Kimura S, Roberts A, Metcalf D, Alexander W. Hematopoietic stem cell deficiencies in mice lacking c-Mpl, the receptor for thrombopoietin. Proc Natl Acad Sci U S A. 1998;95:1195-200 pubmed
    ..However, analysis of mice lacking either the cytokine or its receptor, c-Mpl, also revealed deficiencies in progenitor cells of multiple hematopoietic lineages, suggesting that TPO signaling ..
  8. Bunting S, Widmer R, Lipari T, Rangell L, Steinmetz H, Carver Moore K, et al. Normal platelets and megakaryocytes are produced in vivo in the absence of thrombopoietin. Blood. 1997;90:3423-9 pubmed
    ..These studies are in contrast to results observed in vivo in mice deficient in the TPO or c-mpl gene (TPO-/- and c-mpl-/-)...
  9. Amano H, Hackett N, Rafii S, Crystal R. Thrombopoietin gene transfer-mediated enhancement of angiogenic responses to acute ischemia. Circ Res. 2005;97:337-45 pubmed
    ..of thrombopoietin (TPO) functioning to activate megakaryocyte differentiation and platelet release through the c-mpl receptor...

More Information

Publications89

  1. Alexander W, Roberts A, Nicola N, Li R, Metcalf D. Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl. Blood. 1996;87:2162-70 pubmed
    Mice with a null mutation in the thrombopoietin (TPO) receptor c-Mpl were generated by gene targeting. c-mpl-deficient mice developed normally but were deficient in megakaryocytes and severely thrombocytopenic...
  2. Alexander W. Thrombopoietin and the c-Mpl receptor: insights from gene targeting. Int J Biochem Cell Biol. 1999;31:1027-35 pubmed
    ..Through the application of gene targeting technology, the production of mice lacking TPO or its receptor c-Mpl has provided valuable insights into the physiological roles of TPO signalling...
  3. Gurney A, Carver Moore K, de Sauvage F, Moore M. Thrombocytopenia in c-mpl-deficient mice. Science. 1994;265:1445-7 pubmed
    ..The receptor for TPO is c-Mpl. To further investigate the role and specificity of this receptor in regulating megakaryocytopoiesis, c-mpl-..
  4. Winter O, Moser K, Mohr E, Zotos D, Kaminski H, Szyska M, et al. Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow. Blood. 2010;116:1867-75 pubmed publisher
    ..numbers of immature and mature plasma cells are found in the bone marrow of mice deficient for the thrombopoietin receptor (c-mpl) that show impaired megakaryopoiesis...
  5. Drachman J, Griffin J, Kaushansky K. The c-Mpl ligand (thrombopoietin) stimulates tyrosine phosphorylation of Jak2, Shc, and c-Mpl. J Biol Chem. 1995;270:4979-82 pubmed
    c-Mpl is a member of the cytokine receptor superfamily, expressed primarily on hematopoietic cells. Recently, the c-Mpl ligand was cloned and found to have thrombopoietic activity...
  6. Jin D, Shido K, Kopp H, Petit I, Shmelkov S, Young L, et al. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nat Med. 2006;12:557-67 pubmed
    ..was detected in sKitL-deficient Mmp9-/- as well as thrombocytopenic Thpo-/- and TPO receptor-deficient (Mpl-/-) mice...
  7. Carpinelli M, Hilton D, Metcalf D, Antonchuk J, Hyland C, Mifsud S, et al. Suppressor screen in Mpl-/- mice: c-Myb mutation causes supraphysiological production of platelets in the absence of thrombopoietin signaling. Proc Natl Acad Sci U S A. 2004;101:6553-8 pubmed
    ..regulating platelet production, we have executed a large-scale modifier screen with genetically thrombocytopenic Mpl(-/-) mice by using N-ethyl-N-nitrosourea mutagenesis...
  8. Majewski I, Blewitt M, de Graaf C, McManus E, Bahlo M, Hilton A, et al. Polycomb repressive complex 2 (PRC2) restricts hematopoietic stem cell activity. PLoS Biol. 2008;6:e93 pubmed publisher
    ..are sufficient to ameliorate the stem cell defect and thrombocytopenia present in mice that lack the thrombopoietin receptor (c-Mpl)...
  9. Abkowitz J, Chen J. Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones. Blood. 2007;109:5186-90 pubmed
    ..Our studies of c-Mpl, the cellular receptor for the cytokine thrombopoietin, suggest that c-Mpl does not control HSC numbers, as had ..
  10. Pestina T, Jackson C. Differential role of Stat5 isoforms in effecting hematopoietic recovery induced by Mpl-ligand in lethally myelosuppressed mice. Exp Hematol. 2003;31:1198-205 pubmed
    To determine the role of the c-terminal half of c-Mpl in Mpl-L-induced myeloprotection and the importance of Stat5 isoforms in the survival signaling pathways induced by Mpl ligand...
  11. Drachman J, Miyakawa Y, Luthi J, Dahlen D, Raney A, Geddis A, et al. Studies with chimeric Mpl/JAK2 receptors indicate that both JAK2 and the membrane-proximal domain of Mpl are required for cellular proliferation. J Biol Chem. 2002;277:23544-53 pubmed
    The thrombopoietin (TPO) receptor c-Mpl, like other members of the cytokine receptor superfamily, requires the association and activation of Janus kinases (JAKs) for normal signal transduction...
  12. Chen S, Du C, Shen M, Zhao G, Xu Y, Yang K, et al. Sympathetic stimulation facilitates thrombopoiesis by promoting megakaryocyte adhesion, migration, and proplatelet formation. Blood. 2016;127:1024-35 pubmed publisher
    ..Our data deeply characterize the role of sympathetic stimulation in the regulation of thrombopoiesis and reevaluate its physiopathological implications. ..
  13. de Graaf C, Kauppi M, Baldwin T, Hyland C, Metcalf D, Willson T, et al. Regulation of hematopoietic stem cells by their mature progeny. Proc Natl Acad Sci U S A. 2010;107:21689-94 pubmed publisher
    Thrombopoietin (TPO), acting through its receptor Mpl, has two major physiological roles: ensuring production of sufficient platelets via stimulation of megakaryocyte production and maintaining hematopoietic stem cell (HSC) quiescence...
  14. Ziegler S, Burki K, Skoda R. A 2-kb c-mpl promoter fragment is sufficient to direct expression to the megakaryocytic lineage and sites of embryonic hematopoiesis in transgenic mice. Blood. 2002;100:1072-4 pubmed
    b>Thrombopoietin receptor c-mpl is expressed on hematopoietic progenitors and cells of the megakaryocytic lineage. The c-mpl promoter may, therefore, be useful for directing the expression of transgenes...
  15. Verhagen A, Wallace M, Goradia A, Jones S, Croom H, Metcalf D, et al. A kinase-dead allele of Lyn attenuates autoimmune disease normally associated with Lyn deficiency. J Immunol. 2009;182:2020-9 pubmed publisher
    ..Furthermore, our results provide evidence for an additional role for Lyn kinase, distinct from its catalytic activity, in regulating intracellular signaling pathways. ..
  16. Favale F, Messaoudi K, Varghese L, Boukour S, Pecquet C, Gryshkova V, et al. An incomplete trafficking defect to the cell-surface leads to paradoxical thrombocytosis for human and murine MPL P106L. Blood. 2016;128:3146-3158 pubmed publisher
    The mechanisms behind the hereditary thrombocytosis induced by the thrombopoietin (THPO) receptor MPL P106L mutant remain unknown...
  17. Tong W, Lodish H. Lnk inhibits Tpo-mpl signaling and Tpo-mediated megakaryocytopoiesis. J Exp Med. 2004;200:569-80 pubmed
    ..Tpo signaling through its receptor, c-mpl, activates multiple pathways including signal transducer and activator of transcription (STAT)3, STAT5, ..
  18. Kieran M, Perkins A, Orkin S, Zon L. Thrombopoietin rescues in vitro erythroid colony formation from mouse embryos lacking the erythropoietin receptor. Proc Natl Acad Sci U S A. 1996;93:9126-31 pubmed
    ..peripheral blood, and fetal liver demonstrated near normal transcripts levels for EKLF, thrombopoietin (Tpo), c-MPL, GATA-1, GATA-2, and alpha- and embryonic beta H1-globin but non for adult beta maj-globin...
  19. Looney M, Nguyen J, Hu Y, Van Ziffle J, Lowell C, Matthay M. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. J Clin Invest. 2009;119:3450-61 pubmed publisher
    ..Furthermore, our data offer an explanation for the increased incidence of TRALI in patients with immune priming conditions, and we suggest what we believe to be a novel therapeutic approach. ..
  20. Liu H, Zhao Z, Zhong Y, Shan Y, Sun X, Mao B, et al. Identification of a new Mpl-interacting protein, Atp5d. Mol Cell Biochem. 2014;391:85-94 pubmed publisher
    Thrombopoietin (TPO) can regulate hematopoiesis and megakaryopoiesis via activation of its receptor, c-Mpl, and multiple downstream signal transduction pathways...
  21. de Laval B, Pawlikowska P, Barbieri D, Besnard Guerin C, Cico A, Kumar R, et al. Thrombopoietin promotes NHEJ DNA repair in hematopoietic stem cells through specific activation of Erk and NF-?B pathways and their target, IEX-1. Blood. 2014;123:509-19 pubmed publisher
    ..Iex-1 forms a complex with pERK and the catalytic subunit of DNA-PK, which is necessary and sufficient to promote TPO-increased DNA-PK activation and NHEJ DSB repair in both mouse and human HSPCs. ..
  22. Bersenev A, Wu C, Balcerek J, Tong W. Lnk controls mouse hematopoietic stem cell self-renewal and quiescence through direct interactions with JAK2. J Clin Invest. 2008;118:2832-44 pubmed publisher
    ..initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls HSC homeostasis and self-renewal...
  23. Loughran S, Kruse E, Hacking D, de Graaf C, Hyland C, Willson T, et al. The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells. Nat Immunol. 2008;9:810-9 pubmed publisher
    ..We show that Erg is required for definitive hematopoiesis, adult hematopoietic stem cell function and the maintenance of normal peripheral blood platelet numbers. ..
  24. Vigon I, Florindo C, Fichelson S, Guenet J, Mattei M, Souyri M, et al. Characterization of the murine Mpl proto-oncogene, a member of the hematopoietic cytokine receptor family: molecular cloning, chromosomal location and evidence for a function in cell growth. Oncogene. 1993;8:2607-15 pubmed
    The v-mpl oncogene transduced in the myeloproliferative leukemia virus (MPLV) encodes a truncated form of a putative receptor protein that belongs to the cytokine receptor superfamily...
  25. Murone M, Carpenter D, de Sauvage F. Hematopoietic deficiencies in c-mpl and TPO knockout mice. Stem Cells. 1998;16:1-6 pubmed
    Thrombopoietin (TPO) is the primary regulatory of megakaryocyte (Meg) and platelet production. Its receptor, c-mpl, is a member of the cytokine receptor superfamily...
  26. Levin J, Cocault L, Demerens C, Challier C, Pauchard M, Caen J, et al. Thrombocytopenic c-mpl(-/-) mice can produce a normal level of platelets after administration of 5-fluorouracil: the effect of age on the response. Blood. 2001;98:1019-27 pubmed
    ..Mice lacking Mpl, the receptor for thrombopoietin (TPO), are thrombocytopenic...
  27. Takyar S, Vasavada H, Zhang J, Ahangari F, Niu N, Liu Q, et al. VEGF controls lung Th2 inflammation via the miR-1-Mpl (myeloproliferative leukemia virus oncogene)-P-selectin axis. J Exp Med. 2013;210:1993-2010 pubmed publisher
    ..Using mRNA arrays, Argonaute pull-down assays, luciferase expression assays, and mutational analysis, we identified Mpl as a direct target of miR-1 and showed that VEGF controls the expression of endothelial Mpl during Th2 inflammation ..
  28. Gery S, Gueller S, Chumakova K, Kawamata N, Liu L, Koeffler H. Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders. Blood. 2007;110:3360-4 pubmed
    Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients...
  29. Defour J, Itaya M, Gryshkova V, Brett I, Pecquet C, Sato T, et al. Tryptophan at the transmembrane-cytosolic junction modulates thrombopoietin receptor dimerization and activation. Proc Natl Acad Sci U S A. 2013;110:2540-5 pubmed publisher
    Dimerization of single-pass membrane receptors is essential for activation. In the human thrombopoietin receptor (TpoR), a unique amphipathic RWQFP motif separates the transmembrane (TM) and intracellular domains...
  30. Stoffel R, Ziegler S, Ghilardi N, Ledermann B, de Sauvage F, Skoda R. Permissive role of thrombopoietin and granulocyte colony-stimulating factor receptors in hematopoietic cell fate decisions in vivo. Proc Natl Acad Sci U S A. 1999;96:698-702 pubmed
    ..and their receptors in hematopoietic cell fate decisions, we used homologous recombination to replace the thrombopoietin receptor gene (mpl) with a chimeric construct encoding the extracellular domain of mpl and the cytoplasmic domain ..
  31. Vainchenker W, Methia N, Debili N, Titeux M, Wendling F. c-mpl, the thrombopoietin receptor. Thromb Haemost. 1995;74:526-8 pubmed
    v-mpl is a mouse oncogene that is part of the genome of the myeloproliferative leukemia virus (MPLV)...
  32. Pang L, Xue H, Szalai G, Wang X, Wang Y, Watson D, et al. Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins. Blood. 2006;108:2198-206 pubmed
    ..In concert, these data reveal disparate, but overlapping, functions of Ets transcription factors at distinct stages of megakaryocyte maturation. ..
  33. Luc S, Anderson K, Kharazi S, Buza Vidas N, Böiers C, Jensen C, et al. Down-regulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential. Blood. 2008;111:3424-34 pubmed publisher
    ..Herein, residual (1%-2%) MkE potential segregated almost entirely with LSKFlt3hi cells expressing the thrombopoietin receptor (Mpl), whereas LSKFlt3hiMpl- LMPPs lacked significant MkE potential in vitro and in vivo, but sustained ..
  34. Roberts A, Foote S, Alexander W, Scott C, Robb L, Metcalf D. Genetic influences determining progenitor cell mobilization and leukocytosis induced by granulocyte colony-stimulating factor. Blood. 1997;89:2736-44 pubmed
    ..Granulocyte-macrophage colony-stimulating factor (GM-CSF) transgenic, Max41 transgenic, W/Wv, Mpl-null, GM-CSF receptor (beta chain)-null mice, wild-type littermate controls, and six inbred strains of mice were ..
  35. Fleury M, Petit Cocault L, Clay D, Souyri M. Mpl receptor defect leads to earlier appearance of hematopoietic cells/hematopoietic stem cells in the Aorta-Gonad-Mesonephros region, with increased apoptosis. Int J Dev Biol. 2010;54:1067-74 pubmed publisher
    In a previous study, we underlined the functional role of the TPO receptor, Mpl, in the establishment of definitive mouse hematopoiesis, by demonstrating that the lack of Mpl led to a delayed production of definitive hematopoietic cells ..
  36. Millot G, Vainchenker W, Dumenil D, Svinarchuk F. Distinct effects of thrombopoietin depending on a threshold level of activated Mpl in BaF-3 cells. J Cell Sci. 2002;115:2329-37 pubmed
    Thrombopoietin (TPO) plays a critical role in megakaryopoiesis through binding to its receptor Mpl. This involves activation of various intracellular signaling pathways, including phosphoinositide 3-kinase (PI3K) and the mitogen-..
  37. Staerk J, Defour J, Pecquet C, Leroy E, Antoine Poirel H, Brett I, et al. Orientation-specific signalling by thrombopoietin receptor dimers. EMBO J. 2011;30:4398-413 pubmed publisher
    Ligand binding to the thrombopoietin receptor is thought to stabilize an active receptor dimer that regulates megakaryocyte differentiation and platelet formation, as well as haematopoietic stem cell renewal...
  38. Tonelli R, Scardovi A, Pession A, Strippoli P, Bonsi L, Vitale L, et al. Compound heterozygosity for two different amino-acid substitution mutations in the thrombopoietin receptor (c-mpl gene) in congenital amegakaryocytic thrombocytopenia (CAMT). Hum Genet. 2000;107:225-33 pubmed
    ..Recently, two heterozygous truncating mutations of the thrombopoietin (TPO) receptor MPL, coded by the c-mpl gene, were identified in a 10-year-old Japanese patient with CAMT transmitted in an autosomal ..
  39. Luoh S, Stefanich E, Solar G, Steinmetz H, Lipari T, Pestina T, et al. Role of the distal half of the c-Mpl intracellular domain in control of platelet production by thrombopoietin in vivo. Mol Cell Biol. 2000;20:507-15 pubmed
    ..TPO exerts its effect through activation of the c-Mpl receptor and of multiple downstream signal transduction pathways...
  40. Shivdasani R, Rosenblatt M, Zucker Franklin D, Jackson C, Hunt P, Saris C, et al. Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell. 1995;81:695-704 pubmed
    ..These findings provide insight into the genetic analysis of megakaryocyte maturation and thrombopoiesis. ..
  41. Yamaguchi Y, Zon L, Ackerman S, Yamamoto M, Suda T. Forced GATA-1 expression in the murine myeloid cell line M1: induction of c-Mpl expression and megakaryocytic/erythroid differentiation. Blood. 1998;91:450-7 pubmed
    ..Because the c-mpl ligand, thrombopoietin, plays an important role in megakaryopoiesis, the expression of c-mpl and c-mpl ligand (..
  42. McMorran B, Marshall V, de Graaf C, Drysdale K, Shabbar M, Smyth G, et al. Platelets kill intraerythrocytic malarial parasites and mediate survival to infection. Science. 2009;323:797-800 pubmed publisher
    ..These results indicate a protective function for platelets in the early stages of erythrocytic infection distinct from their role in cerebral malaria. ..
  43. Warden C, Davis R, Yoon M, Hui D, Svenson K, Xia Y, et al. Chromosomal localization of lipolytic enzymes in the mouse: pancreatic lipase, colipase, hormone-sensitive lipase, hepatic lipase, and carboxyl ester lipase. J Lipid Res. 1993;34:1451-5 pubmed
    ..Comparison of chromosomal locations for these genes in mouse and humans shows that the previously observed interspecies syntenies are preserved. ..
  44. Labosky P, Winnier G, Sasaki H, Blessing M, Hogan B. The chromosomal mapping of four genes encoding winged helix proteins expressed early in mouse development. Genomics. 1996;34:241-5 pubmed
    ..Since Mf3 is located in a region of Chromosome 9 containing many well-characterized mouse mutations such as short ear (se), ashen (ash), and dilute (d), we have analyzed deletion mutants to determine the location of Mf3 more precisely. ..
  45. Wendling F, Penciolelli J, Charon M, Tambourin P. Factor-independent erythropoietic progenitor cells in leukemia induced by the myeloproliferative leukemia virus. Blood. 1989;73:1161-7 pubmed
    ..Furthermore, the data show that abnormal erythropoiesis was due to the replication defective MPLV information and was not influenced by the Fv-2 locus. ..
  46. Cheng Y, Chikwava K, Wu C, Zhang H, Bhagat A, Pei D, et al. LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors. J Clin Invest. 2016;126:1267-81 pubmed publisher
  47. Chachoua I, Pecquet C, El Khoury M, Nivarthi H, Albu R, Marty C, et al. Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants. Blood. 2016;127:1325-35 pubmed publisher
    ..biochemical, and primary cell assays that the pathogenic CALR mutants specifically activate the thrombopoietin receptor (TpoR/MPL)...
  48. Marty C, Pecquet C, Nivarthi H, El Khoury M, Chachoua I, Tulliez M, et al. Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis. Blood. 2016;127:1317-24 pubmed publisher
    ..demonstrated that the CALR mutants, but not CALRdelex9, specifically activate the thrombopoietin (TPO) receptor (MPL) to induce constitutive activation of Janus kinase 2 and signal transducer and activator of transcription 5/3/1...
  49. Storan M, Heazlewood S, Heazlewood C, Haylock D, Alexander W, Neaves R, et al. Brief Report: Factors Released by Megakaryocytes Thrombin Cleave Osteopontin to Negatively Regulate Hematopoietic Stem Cells. Stem Cells. 2015;33:2351-7 pubmed publisher
    ..Importantly, mice devoid of the myeloproliferative leukemia protein (Mpl), c-Mpl(-/-) mice, contain only approximately 10% of normal megakaryocyte numbers, showed ..
  50. Du J, Wang J, Kong G, Jiang J, Zhang J, Liu Y, et al. Signaling profiling at the single-cell level identifies a distinct signaling signature in murine hematopoietic stem cells. Stem Cells. 2012;30:1447-54 pubmed publisher
    ..Our study of HSC signaling at the homeostasis stage paves the way to investigate signaling changes in HSCs under conditions of stress, aging, and hematopoietic diseases. ..
  51. Hoffmann O, Rung O, Im A, Freyer D, Zhang J, Held J, et al. Thrombopoietin contributes to neuronal damage in experimental bacterial meningitis. Infect Immun. 2011;79:928-36 pubmed publisher
    Thrombopoietin (Tpo), which primarily regulates megakaryopoiesis, and its receptor (c-Mpl) are expressed in the brain, where Tpo exhibits proapototic effects on neurons...
  52. Bernier G, Mathieu M, De Repentigny Y, Vidal S, Kothary R. Cloning and characterization of mouse ACF7, a novel member of the dystonin subfamily of actin binding proteins. Genomics. 1996;38:19-29 pubmed
    ..To determine whether spontaneous mutants that may be defective in mACF7 exist, we have mapped the mACF7 gene to mouse chromosome 4. ..
  53. Antonchuk J, Hyland C, Hilton D, Alexander W. Synergistic effects on erythropoiesis, thrombopoiesis, and stem cell competitiveness in mice deficient in thrombopoietin and steel factor receptors. Blood. 2004;104:1306-13 pubmed
    ..factor (SF) cytokine pathways in the regulation of hematopoiesis was investigated by generating mice lacking both c-Mpl and fully functional c-Kit receptors...
  54. Greig K, Antonchuk J, Metcalf D, Morgan P, Krebs D, Zhang J, et al. Agm1/Pgm3-mediated sugar nucleotide synthesis is essential for hematopoiesis and development. Mol Cell Biol. 2007;27:5849-59 pubmed
  55. Kaushansky K, Broudy V, Lin N, Jorgensen M, McCarty J, Fox N, et al. Thrombopoietin, the Mp1 ligand, is essential for full megakaryocyte development. Proc Natl Acad Sci U S A. 1995;92:3234-8 pubmed
    ..Thus, our results strongly suggest that Tpo is the primary regulator of MK development and platelet production. ..
  56. Coers J, Ranft C, Skoda R. A truncated isoform of c-Mpl with an essential C-terminal peptide targets the full-length receptor for degradation. J Biol Chem. 2004;279:36397-404 pubmed
    Thrombopoietin and its cognate receptor c-Mpl are the primary regulators of megakaryopoiesis and platelet production. They also play an important role in the maintenance of hematopoietic stem cells...
  57. Broudy V, Kaushansky K. Thrombopoietin, the c-mpl ligand, is a major regulator of platelet production. J Leukoc Biol. 1995;57:719-25 pubmed
    ..By using strategies based on the c-mpl receptor, several groups have recently succeeded in purifying and cloning thrombopoietin [1-6]...
  58. Rozenova K, Jiang J, Donaghy R, Aressy B, Greenberg R, Tong W. MERIT40 deficiency expands hematopoietic stem cell pools by regulating thrombopoietin receptor signaling. Blood. 2015;125:1730-8 pubmed publisher
    ..to Tpo stimulation and the stem cell phenotypes are abrogated on a background null for the Tpo receptor Mpl. These results establish M40-containing DUB complexes as novel HSC regulators of HSC expansion, implicate Lys63 ..
  59. Gainsford T, Roberts A, Kimura S, Metcalf D, Dranoff G, Mulligan R, et al. Cytokine production and function in c-mpl-deficient mice: no physiologic role for interleukin-3 in residual megakaryocyte and platelet production. Blood. 1998;91:2745-52 pubmed
    Mice lacking thrombopoietin (TPO), or its receptor c-Mpl, display defective megakaryocyte and platelet development and deficiencies in progenitor cells of multiple hematopoietic lineages...
  60. Ng A, Kauppi M, Metcalf D, Di Rago L, Hyland C, Alexander W. Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential. Proc Natl Acad Sci U S A. 2012;109:2364-9 pubmed publisher
  61. Gaur M, Murphy G, deSauvage F, Leavitt A. Characterization of Mpl mutants using primary megakaryocyte-lineage cells from mpl(-/-) mice: a new system for Mpl structure-function studies. Blood. 2001;97:1653-61 pubmed
    b>Mpl is the thrombopoietin (TPO) receptor...
  62. Coupland L, Cromer D, Davenport M, Parish C. A novel fluorescent-based assay reveals that thrombopoietin signaling and Bcl-X(L) influence, respectively, platelet and erythrocyte lifespans. Exp Hematol. 2010;38:453-461.e1 pubmed publisher
    ..Control, c-mpl knockout (KO), and Bcl-X(L) mutant mice were injected with CFSE and platelet and erythrocyte fluorescence followed ..
  63. Potts K, Sargeant T, Dawson C, Josefsson E, Hilton D, Alexander W, et al. Mouse prenatal platelet-forming lineages share a core transcriptional program but divergent dependence on MPL. Blood. 2015;126:807-16 pubmed publisher
    ..appear? Do pathogenic genetic lesions of adult MKs affect DPFCs? What role does myeloproliferative leukemia virus (MPL), a key regulator of adult megakaryopoiesis, play in prenatal platelet-forming lineages? We performed a ..
  64. Nishikawa S, Arai S, Masamoto Y, Kagoya Y, Toya T, Watanabe Okochi N, et al. Thrombopoietin/MPL signaling confers growth and survival capacity to CD41-positive cells in a mouse model of Evi1 leukemia. Blood. 2014;124:3587-96 pubmed publisher
    ..identified that the expression of megakaryocytic surface molecules such as ITGA2B (CD41) and the THPO receptor, MPL, positively correlates with EVI1 expression in AML patients...
  65. Hart A, Melet F, Grossfeld P, Chien K, Jones C, Tunnacliffe A, et al. Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia. Immunity. 2000;13:167-77 pubmed
    ..We map the megakaryocytic defects in 14 Jacobsen patients to a minimal region on 11q that includes the Fli-1 gene and suggest that dysmegakaryopoiesis in these patients may be caused by hemizygous loss of Fli-1. ..
  66. Miyakawa Y, Drachman J, Gallis B, Kaushansky A, Kaushansky K. A structure-function analysis of serine/threonine phosphorylation of the thrombopoietin receptor, c-Mpl. J Biol Chem. 2000;275:32214-9 pubmed
    Thrombopoietin (TPO), the critical regulator of platelet production, acts by binding to its cell surface receptor, c-Mpl. Numerous studies have shown that TPO binding leads to JAK2 kinase activation and Tyr phosphorylation of c-Mpl and ..
  67. Satoh Y, Matsumura I, Tanaka H, Ezoe S, Fukushima K, Tokunaga M, et al. AML1/RUNX1 works as a negative regulator of c-Mpl in hematopoietic stem cells. J Biol Chem. 2008;283:30045-56 pubmed publisher
    In this study, we analyzed the roles for AML1/RUNX1 in the regulation of the c-mpl promoter. Wild-type AML1 activated the c-mpl promoter through the proximal AML-binding site in luciferase assays using 293T and HeLa cells...
  68. Meijome T, Baughman J, Hooker R, Cheng Y, Ciovacco W, Balamohan S, et al. C-Mpl Is Expressed on Osteoblasts and Osteoclasts and Is Important in Regulating Skeletal Homeostasis. J Cell Biochem. 2016;117:959-69 pubmed publisher
    C-Mpl is the receptor for thrombopoietin (TPO), the main megakaryocyte (MK) growth factor, and c-Mpl is believed to be expressed on cells of the hematopoietic lineage...
  69. Köhler A, De Filippo K, Hasenberg M, van den Brandt C, Nye E, Hosking M, et al. G-CSF-mediated thrombopoietin release triggers neutrophil motility and mobilization from bone marrow via induction of Cxcr2 ligands. Blood. 2011;117:4349-57 pubmed publisher
    ..Thus, a network of signaling molecules, chemokines, and cells controls neutrophil release from the BM, and their mobilization involves rapidly induced Cxcr2-mediated motility controlled by TPO as a pacemaker. ..
  70. Ivanova A, Wuerfel J, Zhang J, Hoffmann O, Ballmaier M, Dame C. Expression pattern of the thrombopoietin receptor (Mpl) in the murine central nervous system. BMC Dev Biol. 2010;10:77 pubmed publisher
    Thrombopoietin (Thpo) and its receptor (Mpl), which regulate megakaryopoiesis, are expressed in the central nervous system (CNS), where Thpo is thought to exert pro-apoptotic effects on newly generated neurons...
  71. Tan W, Liu B, Barsoum A, Huang W, Kolls J, Schwarzenberger P. Requirement of TPO/c-mpl for IL-17A-induced granulopoiesis and megakaryopoiesis. J Leukoc Biol. 2013;94:1303-8 pubmed publisher
    ..investigated the effects of in vivo expression of IL-17A on granulopoiesis and megakaryopoiesis in TPO receptor c-mpl-/- mice. IL-17A expression expanded megakaryocytes by 2...
  72. Ye T, Gordon C, Lai Y, Fujiwara Y, Peters L, Perkins A, et al. Ermap, a gene coding for a novel erythroid specific adhesion/receptor membrane protein. Gene. 2000;242:337-45 pubmed
    ..Northern blot analysis and in-situ hybridization demonstrated that Ermap expression was restricted to fetal and adult erythroid tissues. ERMAP is likely a novel adhesion/receptor molecule specific for erythroid cells. ..
  73. Sangkhae V, Etheridge S, Kaushansky K, Hitchcock I. The thrombopoietin receptor, MPL, is critical for development of a JAK2V617F-induced myeloproliferative neoplasm. Blood. 2014;124:3956-63 pubmed publisher
    ..Here we show that loss of the thrombopoietin (TPO) receptor (MPL) significantly ameliorates MPN development in JAK2V617F(+) transgenic mice, whereas loss of TPO only mildly affects ..
  74. Stumpo D, Broxmeyer H, Ward T, Cooper S, Hangoc G, Chung Y, et al. Targeted disruption of Zfp36l2, encoding a CCCH tandem zinc finger RNA-binding protein, results in defective hematopoiesis. Blood. 2009;114:2401-10 pubmed publisher
    ..These data establish Zfp36l2 as a critical modulator of definitive hematopoiesis and suggest a novel regulatory pathway involving control of mRNA stability in the life cycle of hematopoietic stem and progenitor cells. ..
  75. Frohlich L, Liu Z, Beier D, Lanske B. Genomic structure and refined chromosomal localization of the mouse Ptch2 gene. Cytogenet Genome Res. 2002;97:106-10 pubmed
    ..Single-strand conformation polymorphism analysis was used to map mouse Ptch2 to chromosome 4 between the microsatellite markers D4Mit20 and D4Mit334. ..
  76. Ng A, Kauppi M, Metcalf D, Hyland C, Josefsson E, Lebois M, et al. Mpl expression on megakaryocytes and platelets is dispensable for thrombopoiesis but essential to prevent myeloproliferation. Proc Natl Acad Sci U S A. 2014;111:5884-9 pubmed publisher
    ..TPO) acting via its receptor, the cellular homologue of the myeloproliferative leukemia virus oncogene (Mpl), is the major cytokine regulator of platelet number...
  77. Saur S, Sangkhae V, Geddis A, Kaushansky K, Hitchcock I. Ubiquitination and degradation of the thrombopoietin receptor c-Mpl. Blood. 2010;115:1254-63 pubmed publisher
    ..Thrombopoietin (Tpo), acting through its receptor c-Mpl, is required for hematopoietic stem cell maintenance and megakaryopoiesis...
  78. Ku H, Hirayama F, Kato T, Miyazaki H, Aritomi M, Ota Y, et al. Soluble thrombopoietin receptor (Mpl) and granulocyte colony-stimulating factor receptor directly stimulate proliferation of primitive hematopoietic progenitors of mice in synergy with steel factor or the ligand for Flt3/Flk2. Blood. 1996;88:4124-31 pubmed
    ..The direct effects of the soluble receptors appear to be mediated through interactions with their respective membrane-bound receptors expressed on the primitive hematopoietic progenitors. ..
  79. Tiedt R, Coers J, Ziegler S, Wiestner A, Hao Shen H, Bornmann C, et al. Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes. Blood. 2009;113:1768-77 pubmed publisher
    We generated mice expressing a full-length Mpl transgene under the control of a 2-kb Mpl promoter in an Mpl(-/-) background, effectively obtaining mice that express full-length Mpl in the absence of other Mpl isoforms...
  80. Varghese L, Zhang J, Young S, Willson T, Alexander W, Nicola N, et al. Functional characterization of c-Mpl ectodomain mutations that underlie congenital amegakaryocytic thrombocytopenia. Growth Factors. 2014;32:18-26 pubmed publisher
    Activation of the cell surface receptor, c-Mpl, by the cytokine, thrombopoietin (TPO), underpins megakaryocyte and platelet production in mammals...