User menu

The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by Ligand, Mutations, Agonists, and Mutated Calreticulin.

Bibliographic reference Varghese, Leila ; Defour, Jean-Philippe ; Pecquet, Christian ; Constantinescu, Stefan N.. The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by Ligand, Mutations, Agonists, and Mutated Calreticulin.. In: Frontiers in Endocrinology, Vol. 8, p. 59 (2017)
Permanent URL http://hdl.handle.net/2078.1/191425
  1. Vigon I., Mornon J. P., Cocault L., Mitjavila M. T., Tambourin P., Gisselbrecht S., Souyri M., Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene: identification of a member of the hematopoietic growth factor receptor superfamily., 10.1073/pnas.89.12.5640
  2. Lok Si, Kaushansky Kenneth, Holly Richard D., Kuijper Joseph L., Lofton-Day Catherine E., Oort Pieter J., Grant Francis J., Heipel Mark D., Burkhead Steve K., Kramer Janet M., Bell L. Anne, Sprecher Cindy A., Blumberg Hal, Johnson Rebecca, Prunkard Donna, Ching Andrew F. T., Mathewes Shannon L., Bailey Mason C., Forstrom John W., Buddle Michele M., Osborn Sherri G., Evans Simon J., Sheppard Paul O., Presnell Scott R., O'Hara Patrick J., Hagen Fredrick S., Roth Gerald J., Foster Donald C., Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo, 10.1038/369565a0
  3. de Sauvage Frederic J., Hass Philip E., Spencer Susan D., Malloy Beth E., Gurney Austin L., Spencer Steven A., Darbonne Walter C., Henzel William J., Wong Suzy C., Kuang Wun-Jing, Oles Karl J., Hultgren Bruce, Solberg Lawrence A., Goeddel David V., Eaton Dan L., Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand, 10.1038/369533a0
  4. Bartley T, Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor MpI, 10.1016/0092-8674(94)90450-2
  5. Sohma Yoshiaki, Akahori Hiromichi, Seki Naohiko, Hori Tada-aki, Ogami Kinya, Kato Takashi, Shimada Yoshihiro, Kawamura Kazuo, Miyazaki Hiroshi, Molecular cloning and chromosomal localization of the human thrombopoietin gene, 10.1016/0014-5793(94)01008-0
  6. Foster D. C., Sprecher C. A., Grant F. J., Kramer J. M., Kuijper J. L., Holly R. D., Whitmore T. E., Heipel M. D., Bell L. A., Ching A. F., Human thrombopoietin: gene structure, cDNA sequence, expression, and chromosomal localization., 10.1073/pnas.91.26.13023
  7. Wendling Françoise, Maraskovsky Eugene, Debili Najet, Florindo Christina, Teepe Mark, Titeux Monique, Methia Nassia, Breton-Gorius Janine, Cosman David, Vainchenker William, c-Mpl ligand is a humoral regulator of megakaryocytopoiesis, 10.1038/369571a0
  8. Ezumi Yasuharu, Takayama Hiroshi, Okuma Minoru, Thrombopoietin, c-Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and STAT3, and enhances agonists-induced aggregation in platelets in vitro, 10.1016/0014-5793(95)01072-m
  9. Morita Haruhiko, Tahara Tomoyuki, Matsumoto Atsushi, Kato Takashi, Miyazaki Hiroshi, Ohashi Hideya, Functional analysis of the cytoplastic domain of the human Mpl receptor for tyrosine-phosphorylation of the signaling molecules, proliferation and differentiation, 10.1016/0014-5793(96)01047-2
  10. Sattler, Exp Hematol, 23, 1040 (1995)
  11. Drachman Jonathan G., Millett Kelly M., Kaushansky Kenneth, Thrombopoietin Signal Transduction Requires Functional JAK2, Not TYK2, 10.1074/jbc.274.19.13480
  12. Tortolani, Blood, 85, 3444 (1995)
  13. Bacon Chris M., Justin Tortolani P., Shimosaka Akihiro, Rees Robert C., Longo Dan L., O'Shea John J., Thrombopoietin (TPO) induces tyrosine phosphorylation and activation of STAT5 and STAT3, 10.1016/0014-5793(95)00796-c
  14. Gurney A. L., Wong S. C., Henzel W. J., de Sauvage F. J., Distinct regions of c-Mpl cytoplasmic domain are coupled to the JAK-STAT signal transduction pathway and Shc phosphorylation., 10.1073/pnas.92.12.5292
  15. Miyakawa, Blood, 87, 439 (1996)
  16. Rojnuckarin, Blood, 94, 1273 (1999)
  17. Geddis Amy E., Fox Norma E., Kaushansky Kenneth, Phosphatidylinositol 3-Kinase Is Necessary but Not Sufficient for Thrombopoietin-induced Proliferation in Engineered Mpl-bearing Cell Lines as Well as in Primary Megakaryocytic Progenitors, 10.1074/jbc.m105178200
  18. Debili, Blood, 85, 391 (1995)
  19. Forsberg E. Camilla, Prohaska Susan S., Katzman Sol, Heffner Garrett C., Stuart Josh M., Weissman Irving L., Differential Expression of Novel Potential Regulators in Hematopoietic Stem Cells, 10.1371/journal.pgen.0010028
  20. Alexander, Blood, 87, 2162 (1996)
  21. de Sauvage F. J., Physiological regulation of early and late stages of megakaryocytopoiesis by thrombopoietin, 10.1084/jem.183.2.651
  22. Gurney A., Carver-Moore K, de Sauvage F., Moore M., Thrombocytopenia in c-mpl-deficient mice, 10.1126/science.8073287
  23. Qian Hong, Buza-Vidas Natalija, Hyland Craig D., Jensen Christina T., Antonchuk Jennifer, Månsson Robert, Thoren Lina A., Ekblom Marja, Alexander Warren S., Jacobsen Sten Eirik W., Critical Role of Thrombopoietin in Maintaining Adult Quiescent Hematopoietic Stem Cells, 10.1016/j.stem.2007.10.008
  24. Yoshihara Hiroki, Arai Fumio, Hosokawa Kentaro, Hagiwara Tetsuya, Takubo Keiyo, Nakamura Yuka, Gomei Yumiko, Iwasaki Hiroko, Matsuoka Sahoko, Miyamoto Kana, Miyazaki Hiroshi, Takahashi Takao, Suda Toshio, Thrombopoietin/MPL Signaling Regulates Hematopoietic Stem Cell Quiescence and Interaction with the Osteoblastic Niche, 10.1016/j.stem.2007.10.020
  25. MURAOKA KENJI, ISHII EIICHI, TSUJI KOHICHIRO, YAMAMOTO SHUICHI, YAMAGUCHI HIDETO, HRA TSHIRO, KOGA HIROYUKI, NAKAHATA TATSUTOSHI, MIYAZAKI SUMIO, Defective response to thrombopoietin and impaired expression of c-mpl mRNA of bone marrow cells in congenital amegakaryocytic thrombocytopenia, 10.1046/j.1365-2141.1997.d01-2028.x
  26. Ballmaier M., c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia, 10.1182/blood.v97.1.139
  27. Ihara K., Ishii E., Eguchi M., Takada H., Suminoe A., Good R. A., Hara T., Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia, 10.1073/pnas.96.6.3132
  28. Ding J., Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin, 10.1182/blood-2003-10-3471
  29. Pikman Yana, Lee Benjamin H, Mercher Thomas, McDowell Elizabeth, Ebert Benjamin L, Gozo Maricel, Cuker Adam, Wernig Gerlinde, Moore Sandra, Galinsky Ilene, DeAngelo Daniel J, Clark Jennifer J, Lee Stephanie J, Golub Todd R, Wadleigh Martha, Gilliland D. Gary, Levine Ross L, MPLW515L Is a Novel Somatic Activating Mutation in Myelofibrosis with Myeloid Metaplasia, 10.1371/journal.pmed.0030270
  30. Pardanani A. D., Levine R. L., Lasho T., Pikman Y., Mesa R. A., Wadleigh M., Steensma D. P., Elliott M. A., Wolanskyj A. P., Hogan W. J., McClure R. F., Litzow M. R., Gilliland D. G., Tefferi A., MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients, 10.1182/blood-2006-04-018879
  31. Malinge S., Ragu C., Della-Valle V., Pisani D., Constantinescu S. N., Perez C., Villeval J.-L., Reinhardt D., Landman-Parker J., Michaux L., Dastugue N., Baruchel A., Vainchenker W., Bourquin J.-P., Penard-Lacronique V., Bernard O. A., Activating mutations in human acute megakaryoblastic leukemia, 10.1182/blood-2008-01-136366
  32. Moliterno A. R., Williams D. M., Gutierrez-Alamillo L. I., Salvatori R., Ingersoll R. G., Spivak J. L., Mpl Baltimore: A thrombopoietin receptor polymorphism associated with thrombocytosis, 10.1073/pnas.0404241101
  33. El-Harith El-Harith Abdelghaffar, Roesl Cornelia, Ballmaier Matthias, Germeshausen Manuela, Frye-Boukhriss Hildegard, von Neuhoff Nils, Becker Christian, Nürnberg Gudrun, Nürnberg Peter, Ahmed Mirghani Ali Mohamed, Hübener Jeannette, Schmidtke Jörg, Welte Karl, Stuhrmann Manfred, Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in theMPLgene, 10.1111/j.1365-2141.2008.07430.x
  34. Kawamata Norihiko, Ogawa Seishi, Yamamoto Go, Lehmann Soren, Levine Ross L., Pikman Yana, Nannya Yasuhito, Sanada Masashi, Miller Carl W., Gilliland D. Gary, Genetic profiling of myeloproliferative disorders by single-nucleotide polymorphism oligonucleotide microarray, 10.1016/j.exphem.2008.06.006
  35. Pietra D., Brisci A., Rumi E., Boggi S., Elena C., Pietrelli A., Bordoni R., Ferrari M., Passamonti F., De Bellis G., Cremonesi L., Cazzola M., Deep sequencing reveals double mutations in cis of MPL exon 10 in myeloproliferative neoplasms, 10.3324/haematol.2010.034793
  36. Seubert Nadine, Royer Yohan, Staerk Judith, Kubatzky Katharina F, Moucadel Virginie, Krishnakumar Shyam, Smith Steven O, Constantinescu Stefan N, Active and Inactive Orientations of the Transmembrane and Cytosolic Domains of the Erythropoietin Receptor Dimer, 10.1016/s1097-2765(03)00389-7
  37. Bazan J. F., Structural design and molecular evolution of a cytokine receptor superfamily., 10.1073/pnas.87.18.6934
  38. Deane Charlotte M., Kroemer Romano T., Richards W. Graham, A structural model of the human thrombopoietin receptor complex, 10.1016/s1093-3263(97)00102-2
  39. Sabath, Blood, 94, 365 (1999)
  40. Souyri Michèle, Vigon Isabelle, Penciolelli Jean-François, Heard Jean-Michel, Tambourin Pierre, Wendling Françoise, A putative truncated cytokine receptor gene transduced by the myeloproliferative leukemia virus immortalizes hematopoietic progenitors, 10.1016/0092-8674(90)90410-g
  41. Fox Norma E., Lim Jihyang, Chen Rose, Geddis Amy E., F104S c-Mpl responds to a transmembrane domain−binding thrombopoietin receptor agonist: Proof of concept that selected receptor mutations in congenital amegakaryocytic thrombocytopenia can be stimulated with alternative thrombopoietic agents, 10.1016/j.exphem.2010.02.007
  42. Varghese Leila N., Zhang Jian-Guo, Young Samuel N., Willson Tracy A., Alexander Warren S., Nicola Nicos A., Babon Jeffrey J., Murphy James M., Functional characterization of c-Mpl ectodomain mutations that underlie congenital amegakaryocytic thrombocytopenia, 10.3109/08977194.2013.874347
  43. Staerk J., An amphipathic motif at the transmembrane-cytoplasmic junction prevents autonomous activation of the thrombopoietin receptor, 10.1182/blood-2005-06-2600
  44. Defour J-P, Chachoua I, Pecquet C, Constantinescu S N, Oncogenic activation of MPL/thrombopoietin receptor by 17 mutations at W515: implications for myeloproliferative neoplasms, 10.1038/leu.2015.271
  45. Defour J.-P., Itaya M., Gryshkova V., Brett I. C., Pecquet C., Sato T., Smith S. O., Constantinescu S. N., Tryptophan at the transmembrane-cytosolic junction modulates thrombopoietin receptor dimerization and activation, 10.1073/pnas.1211560110
  46. Teofili Luciana, Giona Fiorina, Martini Maurizio, Cenci Tonia, Guidi Francesco, Torti Lorenza, Palumbo Giovanna, Amendola Angela, Foà Robin, Larocca Luigi M., Markers of Myeloproliferative Diseases in Childhood Polycythemia Vera and Essential Thrombocythemia, 10.1200/jco.2006.08.6884
  47. Liu K., Martini M., Rocca B., Amos C. I., Teofili L., Giona F., Ding J., Komatsu H., Larocca L. M., Skoda R. C., Evidence for a founder effect of the MPL-S505N mutation in eight Italian pedigrees with hereditary thrombocythemia, 10.3324/haematol.2009.005918
  48. Leroy Emilie, Defour Jean-Philippe, Sato Takeshi, Dass Sharmila, Gryshkova Vitalina, Shwe Myat M., Staerk Judith, Constantinescu Stefan N., Smith Steven O., His499Regulates Dimerization and Prevents Oncogenic Activation by Asparagine Mutations of the Human Thrombopoietin Receptor, 10.1074/jbc.m115.696534
  49. Kim Min-Ju, Park Sang Ho, Opella Stanley J., Marsilje Thomas H., Michellys Pierre-Yves, Seidel H. Martin, Tian Shin-Shay, NMR Structural Studies of Interactions of a Small, Nonpeptidyl Tpo Mimic with the Thrombopoietin Receptor Extracellular Juxtamembrane and Transmembrane Domains, 10.1074/jbc.m611616200
  50. Matthews E. E., Thevenin D., Rogers J. M., Gotow L., Lira P. D., Reiter L. A., Brissette W. H., Engelman D. M., Thrombopoietin receptor activation: transmembrane helix dimerization, rotation, and allosteric modulation, 10.1096/fj.10-178673
  51. Staerk Judith, Defour Jean-Philippe, Pecquet Christian, Leroy Emilie, Antoine-Poirel Hélène, Brett Ian, Itaya Miki, Smith Steven O, Vainchenker William, Constantinescu Stefan N, Orientation-specific signalling by thrombopoietin receptor dimers : Orientation-specific TpoR signalling, 10.1038/emboj.2011.315
  52. Drachman J. G., Kaushansky K., Dissecting the thrombopoietin receptor: Functional elements of the Mpl cytoplasmic domain, 10.1073/pnas.94.6.2350
  53. Hitchcock I. S., Chen M. M., King J. R., Kaushansky K., YRRL motifs in the cytoplasmic domain of the thrombopoietin receptor regulate receptor internalization and degradation, 10.1182/blood-2008-01-134049
  54. Saur S. J., Sangkhae V., Geddis A. E., Kaushansky K., Hitchcock I. S., Ubiquitination and degradation of the thrombopoietin receptor c-Mpl, 10.1182/blood-2009-06-227033
  55. Royer Yohan, Staerk Judith, Costuleanu Marcel, Courtoy Pierre J., Constantinescu Stefan N., Janus Kinases Affect Thrombopoietin Receptor Cell Surface Localization and Stability, 10.1074/jbc.m501376200
  56. Dahlen D. D., Internalization of the thrombopoietin receptor is regulated by 2 cytoplasmic motifs, 10.1182/blood-2002-11-3468
  57. Pecquet C., Diaconu C. C., Staerk J., Girardot M., Marty C., Royer Y., Defour J.-P., Dusa A., Besancenot R., Giraudier S., Villeval J.-L., Knoops L., Courtoy P. J., Vainchenker W., Constantinescu S. N., Thrombopoietin receptor down-modulation by JAK2 V617F: restoration of receptor levels by inhibitors of pathologic JAK2 signaling and of proteasomes, 10.1182/blood-2011-08-372524
  58. Alexander, EMBO J, 15, 6531 (1996)
  59. Pecquet C., Staerk J., Chaligne R., Goss V., Lee K. A., Zhang X., Rush J., Van Hees J., Poirel H. A., Scheiff J.-M., Vainchenker W., Giraudier S., Polakiewicz R. D., Constantinescu S. N., Induction of myeloproliferative disorder and myelofibrosis by thrombopoietin receptor W515 mutants is mediated by cytosolic tyrosine 112 of the receptor, 10.1182/blood-2008-10-183558
  60. Benit, J Virol, 68, 5270 (1994)
  61. Murakami M., Narazaki M., Hibi M., Yawata H., Yasukawa K., Hamaguchi M., Taga T., Kishimoto T., Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family., 10.1073/pnas.88.24.11349
  62. O’Neal, Lymphokine Cytokine Res, 12, 309 (1993)
  63. Constantinescu Stefan N, Huang Lily Jun-shen, Nam Hyung-song, Lodish Harvey F, The Erythropoietin Receptor Cytosolic Juxtamembrane Domain Contains an Essential, Precisely Oriented, Hydrophobic Motif, 10.1016/s1097-2765(01)00185-x
  64. Huang Lily Jun-shen, Constantinescu Stefan N., Lodish Harvey F., The N-Terminal Domain of Janus Kinase 2 Is Required for Golgi Processing and Cell Surface Expression of Erythropoietin Receptor, 10.1016/s1097-2765(01)00401-4
  65. Fukunaga, EMBO J, 10, 2855 (1991)
  66. Sakamaki, EMBO J, 11, 3541 (1992)
  67. Wallweber Heidi J A, Tam Christine, Franke Yvonne, Starovasnik Melissa A, Lupardus Patrick J, Structural basis of recognition of interferon-α receptor by tyrosine kinase 2, 10.1038/nsmb.2807
  68. Ferrao Ryan, Wallweber Heidi J.A., Ho Hoangdung, Tam Christine, Franke Yvonne, Quinn John, Lupardus Patrick J., The Structural Basis for Class II Cytokine Receptor Recognition by JAK1, 10.1016/j.str.2016.03.023
  69. Zhang Di, Wlodawer Alexander, Lubkowski Jacek, Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1, 10.1016/j.jmb.2016.10.005
  70. Richter Marc F., Duménil Guillaume, Uzé Gilles, Fellous Marc, Pellegrini Sandra, Specific Contribution of Tyk2 JH Regions to the Binding and the Expression of the Interferon α/β Receptor Component IFNAR1, 10.1074/jbc.273.38.24723
  71. Zhao Yanming, Wagner Fred, Frank Stuart J., Kraft Andrew S., The Amino-terminal Portion of the JAK2 Protein Kinase Is Necessary For Binding and Phosphorylation of the Granulocyte-Macrophage Colony-stimulating Factor Receptor β Chain, 10.1074/jbc.270.23.13814
  72. Chen M., Cheng A., Chen Y.-Q., Hymel A., Hanson E. P., Kimmel L., Minami Y., Taniguchi T., Changelian P. S., O'Shea J. J., The amino terminus of JAK3 is necessary and sufficient for binding to the common   chain and confers the ability to transmit interleukin 2-mediated signals, 10.1073/pnas.94.13.6910
  73. Radtke Simone, Haan Serge, Jörissen Angela, Hermanns Heike M., Diefenbach Sandra, Smyczek Tanya, Schmitz-VandeLeur Hildegard, Heinrich Peter C., Behrmann Iris, Haan Claude, The Jak1 SH2 Domain Does Not Fulfill a Classical SH2 Function in Jak/STAT Signaling but Plays a Structural Role for Receptor Interaction and Up-regulation of Receptor Surface Expression, 10.1074/jbc.m500822200
  74. James Chloé, Ugo Valérie, Le Couédic Jean-Pierre, Staerk Judith, Delhommeau François, Lacout Catherine, Garçon Loïc, Raslova Hana, Berger Roland, Bennaceur-Griscelli Annelise, Villeval Jean Luc, Constantinescu Stefan N., Casadevall Nicole, Vainchenker William, A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera, 10.1038/nature03546
  75. BAXTER E, SCOTT L, CAMPBELL P, EAST C, FOUROUCLAS N, SWANTON S, VASSILIOU G, BENCH A, BOYD E, CURTIN N, Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders, 10.1016/s0140-6736(05)74230-6
  76. Levine Ross L., Wadleigh Martha, Cools Jan, Ebert Benjamin L., Wernig Gerlinde, Huntly Brian J.P., Boggon Titus J., Wlodarska Iwona, Clark Jennifer J., Moore Sandra, Adelsperger Jennifer, Koo Sumin, Lee Jeffrey C., Gabriel Stacey, Mercher Thomas, D’Andrea Alan, Fröhling Stefan, Döhner Konstanze, Marynen Peter, Vandenberghe Peter, Mesa Ruben A., Tefferi Ayalew, Griffin James D., Eck Michael J., Sellers William R., Meyerson Matthew, Golub Todd R., Lee Stephanie J., Gilliland D. Gary, Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis, 10.1016/j.ccr.2005.03.023
  77. Kralovics Robert, Passamonti Francesco, Buser Andreas S., Teo Soon-Siong, Tiedt Ralph, Passweg Jakob R., Tichelli Andre, Cazzola Mario, Skoda Radek C., A Gain-of-Function Mutation ofJAK2in Myeloproliferative Disorders, 10.1056/nejmoa051113
  78. Vainchenker W, Constantinescu S N, JAK/STAT signaling in hematological malignancies, 10.1038/onc.2012.347
  79. Sangkhae V., Etheridge S. L., Kaushansky K., Hitchcock I. S., The thrombopoietin receptor, MPL, is critical for development of a JAK2V617F-induced myeloproliferative neoplasm, 10.1182/blood-2014-07-587238
  80. Wang Xiaoli, Haylock David, Hu Cing Siang, Kowalczyk Wioleta, Jiang Tianbo, Qiu Jiajing, Mosoyan Goar, He Wu, Marshall Netonia, Mascarenhas John, Tarasova Anna, Brody Joshua, Winkler David, Hoffman Ronald, A thrombopoietin receptor antagonist is capable of depleting myelofibrosis hematopoietic stem and progenitor cells, 10.1182/blood-2015-10-674465
  81. Kimura S., Roberts A. W., Metcalf D., Alexander W. S., Hematopoietic stem cell deficiencies in mice lacking c-Mpl, the receptor for thrombopoietin, 10.1073/pnas.95.3.1195
  82. Qian, Blood, 92, 2189 (1998)
  83. Grozovsky Renata, Begonja Antonija Jurak, Liu Kaifeng, Visner Gary, Hartwig John H, Falet Hervé, Hoffmeister Karin M, The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling, 10.1038/nm.3770
  84. Wolber Eva-Maria, Jelkmann Wolfgang, Interleukin-6 Increases Thrombopoietin Production in Human Hepatoma Cells HepG2 and Hep3B, 10.1089/10799900050023915
  85. Stoffel, Blood, 87, 567 (1996)
  86. Fielder, Blood, 87, 2154 (1996)
  87. Ichikawa, Thromb Haemost, 76, 156 (1996)
  88. Ng A. P., Kauppi M., Metcalf D., Hyland C. D., Josefsson E. C., Lebois M., Zhang J.-G., Baldwin T. M., Di Rago L., Hilton D. J., Alexander W. S., Mpl expression on megakaryocytes and platelets is dispensable for thrombopoiesis but essential to prevent myeloproliferation, 10.1073/pnas.1404354111
  89. Standen Graham, Clench Timothy, Rapid detection of MPL Baltimore using LightCycler®technology and melting curve analysis, 10.1111/j.1365-2141.2008.06984.x
  90. Shkalim-Zemer Vered, Dgany Orly, Krasnov Tanya, Yacobovich Joanne, Tamary Hannah, MPL Baltimore Mutation and Thrombocytosis : Case Report and Literature Review, 10.1097/mph.0b013e318286d54c
  91. Verger Emmanuelle, Teillet France, Conejero Carole, Letort Gil, Chomienne Christine, Giraudier Stephane, Cassinat Bruno, Unexplained thrombocytosis: association of Baltimore polymorphism with germlineMPLnonsense mutation, 10.1111/bjh.13840
  92. Stockklausner C., Klotter A.-C., Dickemann N., Kuhlee I. N., Duffert C. M., Kerber C., Gehring N. H., Kulozik A. E., The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis, 10.1182/blood-2014-07-587170
  93. Favale F., Messaoudi K., Varghese L. N., Boukour S., Pecquet C., Gryshkova V., Defour J. P., Albu R.-I., Bluteau O., Ballerini P., Leverger G., Plo I., Debili N., Raslova H., Favier R., Constantinescu S. N., Vainchenker W., An incomplete trafficking defect to the cell-surface leads to paradoxical thrombocytosis for human and murine MPL P106L, 10.1182/blood-2016-06-722058
  94. Lannutti B. J., Epp A., Roy J., Chen J., Josephson N. C., Incomplete restoration of Mpl expression in the mpl-/- mouse produces partial correction of the stem cell-repopulating defect and paradoxical thrombocytosis, 10.1182/blood-2007-11-124859
  95. Tiedt R., Coers J., Ziegler S., Wiestner A., Hao-Shen H., Bornmann C., Schenkel J., Karakhanova S., de Sauvage F. J., Jackson C. W., Skoda R. C., Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes, 10.1182/blood-2008-03-146084
  96. Moliterno Alison R., Hankins W. David, Spivak Jerry L., Impaired Expression of the Thrombopoietin Receptor by Platelets from Patients with Polycythemia Vera, 10.1056/nejm199802263380903
  97. Girardot M., Pecquet C., Boukour S., Knoops L., Ferrant A., Vainchenker W., Giraudier S., Constantinescu S. N., miR-28 is a thrombopoietin receptor targeting microRNA detected in a fraction of myeloproliferative neoplasm patient platelets, 10.1182/blood-2008-06-165985
  98. Chachoua I., Pecquet C., El-Khoury M., Nivarthi H., Albu R.-I., Marty C., Gryshkova V., Defour J.-P., Vertenoeil G., Ngo A., Koay A., Raslova H., Courtoy P. J., Choong M. L., Plo I., Vainchenker W., Kralovics R., Constantinescu S. N., Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants, 10.1182/blood-2015-11-681932
  99. Balligand T, Achouri Y, Pecquet C, Chachoua I, Nivarthi H, Marty C, Vainchenker W, Plo I, Kralovics R, Constantinescu S N, Pathologic activation of thrombopoietin receptor and JAK2-STAT5 pathway by frameshift mutants of mouse calreticulin, 10.1038/leu.2016.47
  100. Buteau Hélène, Pezet Alain, Ferrag Fatima, Perrot-Applanat Martine, Kelly Paul A., Edery Marc, N-Glycosylation of the Prolactin Receptor Is Not Required for Activation of Gene Transcription but Is Crucial for Its Cell Surface Targeting, 10.1210/mend.12.4.0085
  101. Waetzig Georg H., Chalaris Athena, Rosenstiel Philip, Suthaus Jan, Holland Christin, Karl Nadja, Vallés Uriarte Lorena, Till Andreas, Scheller Jürgen, Grötzinger Joachim, Schreiber Stefan, Rose-John Stefan, Seegert Dirk, N-Linked Glycosylation Is Essential for the Stability but Not the Signaling Function of the Interleukin-6 Signal Transducer Glycoprotein 130, 10.1074/jbc.m109.075952
  102. Ding Dawn Xiao-Hong, Vera Juan Carlos, Heaney Mark L., Golde David W., N-Glycosylation of the Human Granulocyte-Macrophage Colony-stimulating Factor Receptor α Subunit Is Essential for Ligand Binding and Signal Transduction, 10.1074/jbc.270.41.24580
  103. Kamikubo Yuichi, Dellas Claudia, Loskutoff David J., Quigley James P., Ruggeri Zaverio M., Contribution of leptin receptor N-linked glycans to leptin binding, 10.1042/bj20071137
  104. Murphy James M., Soboleva Tatiana A., Mirza Shamaruh, Ford Sally C., Olsen Jane E., Chen Jinglong, Young Ian G., Clarification of the role of N-glycans on the common β-subunit of the human IL-3, IL-5 and GM-CSF receptors and the murine IL-3 β-receptor in ligand-binding and receptor activation, 10.1016/j.cyto.2008.02.010
  105. Albu Roxana I., Constantinescu Stefan N., Extracellular Domain N-Glycosylation Controls Human Thrombopoietin Receptor Cell Surface Levels, 10.3389/fendo.2011.00071
  106. McCaffrey K., Braakman I., Protein quality control at the endoplasmic reticulum, 10.1042/ebc20160003
  107. Klampfl Thorsten, Gisslinger Heinz, Harutyunyan Ashot S., Nivarthi Harini, Rumi Elisa, Milosevic Jelena D., Them Nicole C.C., Berg Tiina, Gisslinger Bettina, Pietra Daniela, Chen Doris, Vladimer Gregory I., Bagienski Klaudia, Milanesi Chiara, Casetti Ilaria Carola, Sant'Antonio Emanuela, Ferretti Virginia, Elena Chiara, Schischlik Fiorella, Cleary Ciara, Six Melanie, Schalling Martin, Schönegger Andreas, Bock Christoph, Malcovati Luca, Pascutto Cristiana, Superti-Furga Giulio, Cazzola Mario, Kralovics Robert, Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms, 10.1056/nejmoa1311347
  108. Nangalia J., Massie C.E., Baxter E.J., Nice F.L., Gundem G., Wedge D.C., Avezov E., Li J., Kollmann K., Kent D.G., Aziz A., Godfrey A.L., Hinton J., Martincorena I., Van Loo P., Jones A.V., Guglielmelli P., Tarpey P., Harding H.P., Fitzpatrick J.D., Goudie C.T., Ortmann C.A., Loughran S.J., Raine K., Jones D.R., Butler A.P., Teague J.W., O'Meara S., McLaren S., Bianchi M., Silber Y., Dimitropoulou D., Bloxham D., Mudie L., Maddison M., Robinson B., Keohane C., Maclean C., Hill K., Orchard K., Tauro S., Du M.-Q., Greaves M., Bowen D., Huntly B.J.P., Harrison C.N., Cross N.C.P., Ron D., Vannucchi A.M., Papaemmanuil E., Campbell P.J., Green A.R., Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2, 10.1056/nejmoa1312542
  109. Marty C., Pecquet C., Nivarthi H., El-Khoury M., Chachoua I., Tulliez M., Villeval J.-L., Raslova H., Kralovics R., Constantinescu S. N., Plo I., Vainchenker W., Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis, 10.1182/blood-2015-11-679571
  110. Elf S., Abdelfattah N. S., Chen E., Perales-Paton J., Rosen E. A., Ko A., Peisker F., Florescu N., Giannini S., Wolach O., Morgan E. A., Tothova Z., Losman J.-A., Schneider R. K., Al-Shahrour F., Mullally A., Mutant Calreticulin Requires Both Its Mutant C-terminus and the Thrombopoietin Receptor for Oncogenic Transformation, 10.1158/2159-8290.cd-15-1434
  111. Araki M., Yang Y., Masubuchi N., Hironaka Y., Takei H., Morishita S., Mizukami Y., Kan S., Shirane S., Edahiro Y., Sunami Y., Ohsaka A., Komatsu N., Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms, 10.1182/blood-2015-09-671172
  112. Han Lijuan, Schubert Claudia, Köhler Johanna, Schemionek Mirle, Isfort Susanne, Brümmendorf Tim H., Koschmieder Steffen, Chatain Nicolas, Calreticulin-mutant proteins induce megakaryocytic signaling to transform hematopoietic cells and undergo accelerated degradation and Golgi-mediated secretion, 10.1186/s13045-016-0275-0
  113. Nivarthi H, Chen D, Cleary C, Kubesova B, Jäger R, Bogner E, Marty C, Pecquet C, Vainchenker W, Constantinescu S N, Kralovics R, Thrombopoietin receptor is required for the oncogenic function of CALR mutants, 10.1038/leu.2016.32
  114. Vadhan-Raj Saroj, Stimulation of Megakaryocyte and Platelet Production by a Single Dose of Recombinant Human Thrombopoietin in Patients with Cancer, 10.7326/0003-4819-126-9-199705010-00001
  115. Kuter David J., In vivo effects of Mpl ligand administration and emerging clinical applications for the Mpl ligands : , 10.1097/00062752-199704030-00002
  116. Li J., Thrombocytopenia caused by the development of antibodies to thrombopoietin, 10.1182/blood.v98.12.3241
  117. Basser R. L., Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor, 10.1182/blood.v99.7.2599
  118. Cwirla S. E., Peptide Agonist of the Thrombopoietin Receptor as Potent as the Natural Cytokine, 10.1126/science.276.5319.1696
  119. Tijssen Marloes R., di Summa Franca, van den Oudenrijn Sonja, Zwaginga Jaap Jan, van der Schoot C. Ellen, Voermans Carlijn, de Haas Masja, Functional analysis of single amino-acid mutations in the thrombopoietin-receptor Mpl underlying congenital amegakaryocytic thrombocytopenia, 10.1111/j.1365-2141.2008.07139.x
  120. Orita T., A novel therapeutic approach for thrombocytopenia by minibody agonist of the thrombopoietin receptor, 10.1182/blood-2004-04-1482
  121. Moraga Ignacio, Wernig Gerlinde, Wilmes Stephan, Gryshkova Vitalina, Richter Christian P., Hong Wan-Jen, Sinha Rahul, Guo Feng, Fabionar Hyna, Wehrman Tom S., Krutzik Peter, Demharter Samuel, Plo Isabelle, Weissman Irving L., Minary Peter, Majeti Ravindra, Constantinescu Stefan N., Piehler Jacob, Garcia K. Christopher, Tuning Cytokine Receptor Signaling by Re-orienting Dimer Geometry with Surrogate Ligands, 10.1016/j.cell.2015.02.011
  122. Constantinescu S. N., Keren T., Socolovsky M., Nam H.-s., Henis Y. I., Lodish H. F., Ligand-independent oligomerization of cell-surface erythropoietin receptor is mediated by the transmembrane domain, 10.1073/pnas.081069198
  123. Brown Richard J, Adams Julian J, Pelekanos Rebecca A, Wan Yu, McKinstry William J, Palethorpe Kathryn, Seeber Ruth M, Monks Thea A, Eidne Karin A, Parker Michael W, Waters Michael J, Model for growth hormone receptor activation based on subunit rotation within a receptor dimer, 10.1038/nsmb977
  124. Ruan Weiming, Becker Verena, Klingmüller Ursula, Langosch Dieter, The Interface between Self-assembling Erythropoietin Receptor Transmembrane Segments Corresponds to a Membrane-spanning Leucine Zipper, 10.1074/jbc.m309311200
  125. Ebie Alexandra Z., Fleming Karen G., Dimerization of the Erythropoietin Receptor Transmembrane Domain in Micelles, 10.1016/j.jmb.2006.11.035
  126. Vainchenker William, Constantinescu Stefan N., Plo Isabelle, Recent advances in understanding myelofibrosis and essential thrombocythemia, 10.12688/f1000research.8081.1
  127. Millot G, Differential signalling of NH2-terminal flag-labelled thrombopoietin receptor activated by TPO or anti-FLAG antibodies, 10.1016/j.cellsig.2003.08.010
  128. Iacobucci Ilaria, Li Yongjin, Roberts Kathryn G., Dobson Stephanie M., Kim Jaeseung C., Payne-Turner Debbie, Harvey Richard C., Valentine Marcus, McCastlain Kelly, Easton John, Yergeau Donald, Janke Laura J., Shao Ying, Chen I-Ming L., Rusch Michael, Zandi Sasan, Kornblau Steven M., Konopleva Marina, Jabbour Elias, Paietta Elisabeth M., Rowe Jacob M., Pui Ching-Hon, Gastier-Foster Julie, Gu Zhaohui, Reshmi Shalini, Loh Mignon L., Racevskis Janis, Tallman Martin S., Wiernik Peter H., Litzow Mark R., Willman Cheryl L., McPherson John D., Downing James R., Zhang Jinghui, Dick John E., Hunger Stephen P., Mullighan Charles G., Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia, 10.1016/j.ccell.2015.12.013