Eintrag weiter verarbeiten
Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors
Gespeichert in:
| Zeitschriftentitel: | Stem Cells |
|---|---|
| Personen und Körperschaften: | , , |
| In: | Stem Cells, 24, 2006, 1, S. 105-114 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Oxford University Press (OUP)
|
| Schlagwörter: |
| author_facet |
Drayer, A. Lyndsay Olthof, Sandra G. M. Vellenga, Edo Drayer, A. Lyndsay Olthof, Sandra G. M. Vellenga, Edo |
|---|---|
| author |
Drayer, A. Lyndsay Olthof, Sandra G. M. Vellenga, Edo |
| spellingShingle |
Drayer, A. Lyndsay Olthof, Sandra G. M. Vellenga, Edo Stem Cells Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors Cell Biology Developmental Biology Molecular Medicine |
| author_sort |
drayer, a. lyndsay |
| spelling |
Drayer, A. Lyndsay Olthof, Sandra G. M. Vellenga, Edo 1066-5099 1549-4918 Oxford University Press (OUP) Cell Biology Developmental Biology Molecular Medicine http://dx.doi.org/10.1634/stemcells.2005-0062 <jats:title>Abstract</jats:title> <jats:p>Thrombopoietin (TPO) is a potent regulator of megakaryopoiesis and stimulates megakaryocyte (MK) progenitor expansion and MK differentiation. In this study, we show that TPO induces activation of the mammalian target of rapamycin (mTOR) signaling pathway, which plays a central role in translational regulation and is required for proliferation of MO7e cells and primary human MK progenitors. Treatment of MO7e cells, human CD34+, and primary MK cells with the mTOR inhibitor rapamycin inhibits TPO-induced cell cycling by reducing cells in S phase and blocking cells in G0/G1. Rapamycin markedly inhibits the clonogenic growth of MK progenitors with high proliferative capacity but does not reduce the formation of small MK colonies. Addition of rapamycin to MK suspension cultures reduces the number of MK cells, but inhibition of mTOR does not significantly affect expression of glycoproteins IIb/IIIa (CD41) and glycoprotein Ib (CD42), nuclear polyploidization levels, cell size, or cell survival. The downstream effectors of mTOR, p70 S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1), are phosphorylated by TPO in a rapamycin- and LY294002-sensitive manner. Part of the effect of the phosphatidyl inositol 3-kinase pathway in regulating megakaryopoiesis may be mediated by the mTOR/S6K/4E-BP1 pathway. In conclusion, these data demonstrate that the mTOR pathway is activated by TPO and plays a critical role in regulating proliferation of MK progenitors, without affecting differentiation or cell survival.</jats:p> Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors Stem Cells |
| doi_str_mv |
10.1634/stemcells.2005-0062 |
| facet_avail |
Online Free |
| finc_class_facet |
Biologie Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTYzNC9zdGVtY2VsbHMuMjAwNS0wMDYy |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTYzNC9zdGVtY2VsbHMuMjAwNS0wMDYy |
| institution |
DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 |
| imprint |
Oxford University Press (OUP), 2006 |
| imprint_str_mv |
Oxford University Press (OUP), 2006 |
| issn |
1066-5099 1549-4918 |
| issn_str_mv |
1066-5099 1549-4918 |
| language |
English |
| mega_collection |
Oxford University Press (OUP) (CrossRef) |
| match_str |
drayer2006mammaliantargetofrapamycinisrequiredforthrombopoietininducedproliferationofmegakaryocyteprogenitors |
| publishDateSort |
2006 |
| publisher |
Oxford University Press (OUP) |
| recordtype |
ai |
| record_format |
ai |
| series |
Stem Cells |
| source_id |
49 |
| title |
Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_unstemmed |
Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_full |
Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_fullStr |
Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_full_unstemmed |
Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_short |
Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_sort |
mammalian target of rapamycin is required for thrombopoietin-induced proliferation of megakaryocyte progenitors |
| topic |
Cell Biology Developmental Biology Molecular Medicine |
| url |
http://dx.doi.org/10.1634/stemcells.2005-0062 |
| publishDate |
2006 |
| physical |
105-114 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Thrombopoietin (TPO) is a potent regulator of megakaryopoiesis and stimulates megakaryocyte (MK) progenitor expansion and MK differentiation. In this study, we show that TPO induces activation of the mammalian target of rapamycin (mTOR) signaling pathway, which plays a central role in translational regulation and is required for proliferation of MO7e cells and primary human MK progenitors. Treatment of MO7e cells, human CD34+, and primary MK cells with the mTOR inhibitor rapamycin inhibits TPO-induced cell cycling by reducing cells in S phase and blocking cells in G0/G1. Rapamycin markedly inhibits the clonogenic growth of MK progenitors with high proliferative capacity but does not reduce the formation of small MK colonies. Addition of rapamycin to MK suspension cultures reduces the number of MK cells, but inhibition of mTOR does not significantly affect expression of glycoproteins IIb/IIIa (CD41) and glycoprotein Ib (CD42), nuclear polyploidization levels, cell size, or cell survival. The downstream effectors of mTOR, p70 S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1), are phosphorylated by TPO in a rapamycin- and LY294002-sensitive manner. Part of the effect of the phosphatidyl inositol 3-kinase pathway in regulating megakaryopoiesis may be mediated by the mTOR/S6K/4E-BP1 pathway. In conclusion, these data demonstrate that the mTOR pathway is activated by TPO and plays a critical role in regulating proliferation of MK progenitors, without affecting differentiation or cell survival.</jats:p> |
| container_issue |
1 |
| container_start_page |
105 |
| container_title |
Stem Cells |
| container_volume |
24 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792336109866319880 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T14:55:14.28Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=Mammalian+Target+of+Rapamycin+Is+Required+for+Thrombopoietin-Induced+Proliferation+of+Megakaryocyte+Progenitors&rft.date=2006-01-01&genre=article&issn=1549-4918&volume=24&issue=1&spage=105&epage=114&pages=105-114&jtitle=Stem+Cells&atitle=Mammalian+Target+of+Rapamycin+Is+Required+for+Thrombopoietin-Induced+Proliferation+of+Megakaryocyte+Progenitors&aulast=Vellenga&aufirst=Edo&rft_id=info%3Adoi%2F10.1634%2Fstemcells.2005-0062&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792336109866319880 |
| author | Drayer, A. Lyndsay, Olthof, Sandra G. M., Vellenga, Edo |
| author_facet | Drayer, A. Lyndsay, Olthof, Sandra G. M., Vellenga, Edo, Drayer, A. Lyndsay, Olthof, Sandra G. M., Vellenga, Edo |
| author_sort | drayer, a. lyndsay |
| container_issue | 1 |
| container_start_page | 105 |
| container_title | Stem Cells |
| container_volume | 24 |
| description | <jats:title>Abstract</jats:title> <jats:p>Thrombopoietin (TPO) is a potent regulator of megakaryopoiesis and stimulates megakaryocyte (MK) progenitor expansion and MK differentiation. In this study, we show that TPO induces activation of the mammalian target of rapamycin (mTOR) signaling pathway, which plays a central role in translational regulation and is required for proliferation of MO7e cells and primary human MK progenitors. Treatment of MO7e cells, human CD34+, and primary MK cells with the mTOR inhibitor rapamycin inhibits TPO-induced cell cycling by reducing cells in S phase and blocking cells in G0/G1. Rapamycin markedly inhibits the clonogenic growth of MK progenitors with high proliferative capacity but does not reduce the formation of small MK colonies. Addition of rapamycin to MK suspension cultures reduces the number of MK cells, but inhibition of mTOR does not significantly affect expression of glycoproteins IIb/IIIa (CD41) and glycoprotein Ib (CD42), nuclear polyploidization levels, cell size, or cell survival. The downstream effectors of mTOR, p70 S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1), are phosphorylated by TPO in a rapamycin- and LY294002-sensitive manner. Part of the effect of the phosphatidyl inositol 3-kinase pathway in regulating megakaryopoiesis may be mediated by the mTOR/S6K/4E-BP1 pathway. In conclusion, these data demonstrate that the mTOR pathway is activated by TPO and plays a critical role in regulating proliferation of MK progenitors, without affecting differentiation or cell survival.</jats:p> |
| doi_str_mv | 10.1634/stemcells.2005-0062 |
| facet_avail | Online, Free |
| finc_class_facet | Biologie, Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTYzNC9zdGVtY2VsbHMuMjAwNS0wMDYy |
| imprint | Oxford University Press (OUP), 2006 |
| imprint_str_mv | Oxford University Press (OUP), 2006 |
| institution | DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275 |
| issn | 1066-5099, 1549-4918 |
| issn_str_mv | 1066-5099, 1549-4918 |
| language | English |
| last_indexed | 2024-03-01T14:55:14.28Z |
| match_str | drayer2006mammaliantargetofrapamycinisrequiredforthrombopoietininducedproliferationofmegakaryocyteprogenitors |
| mega_collection | Oxford University Press (OUP) (CrossRef) |
| physical | 105-114 |
| publishDate | 2006 |
| publishDateSort | 2006 |
| publisher | Oxford University Press (OUP) |
| record_format | ai |
| recordtype | ai |
| series | Stem Cells |
| source_id | 49 |
| spelling | Drayer, A. Lyndsay Olthof, Sandra G. M. Vellenga, Edo 1066-5099 1549-4918 Oxford University Press (OUP) Cell Biology Developmental Biology Molecular Medicine http://dx.doi.org/10.1634/stemcells.2005-0062 <jats:title>Abstract</jats:title> <jats:p>Thrombopoietin (TPO) is a potent regulator of megakaryopoiesis and stimulates megakaryocyte (MK) progenitor expansion and MK differentiation. In this study, we show that TPO induces activation of the mammalian target of rapamycin (mTOR) signaling pathway, which plays a central role in translational regulation and is required for proliferation of MO7e cells and primary human MK progenitors. Treatment of MO7e cells, human CD34+, and primary MK cells with the mTOR inhibitor rapamycin inhibits TPO-induced cell cycling by reducing cells in S phase and blocking cells in G0/G1. Rapamycin markedly inhibits the clonogenic growth of MK progenitors with high proliferative capacity but does not reduce the formation of small MK colonies. Addition of rapamycin to MK suspension cultures reduces the number of MK cells, but inhibition of mTOR does not significantly affect expression of glycoproteins IIb/IIIa (CD41) and glycoprotein Ib (CD42), nuclear polyploidization levels, cell size, or cell survival. The downstream effectors of mTOR, p70 S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1), are phosphorylated by TPO in a rapamycin- and LY294002-sensitive manner. Part of the effect of the phosphatidyl inositol 3-kinase pathway in regulating megakaryopoiesis may be mediated by the mTOR/S6K/4E-BP1 pathway. In conclusion, these data demonstrate that the mTOR pathway is activated by TPO and plays a critical role in regulating proliferation of MK progenitors, without affecting differentiation or cell survival.</jats:p> Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors Stem Cells |
| spellingShingle | Drayer, A. Lyndsay, Olthof, Sandra G. M., Vellenga, Edo, Stem Cells, Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors, Cell Biology, Developmental Biology, Molecular Medicine |
| title | Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_full | Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_fullStr | Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_full_unstemmed | Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_short | Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| title_sort | mammalian target of rapamycin is required for thrombopoietin-induced proliferation of megakaryocyte progenitors |
| title_unstemmed | Mammalian Target of Rapamycin Is Required for Thrombopoietin-Induced Proliferation of Megakaryocyte Progenitors |
| topic | Cell Biology, Developmental Biology, Molecular Medicine |
| url | http://dx.doi.org/10.1634/stemcells.2005-0062 |