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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2011-5-27
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pubmed:abstractText |
Notch signaling is essential for lymphocyte development and is also implicated in myelopoiesis. Notch receptors are modified by O-fucosylation catalyzed by protein O-fucosyltransferase 1 (Pofut1). Fringe enzymes add N-acetylglucosamine to O-fucose and modify Notch signaling by altering the sensitivity of Notch receptors to Notch ligands. To address physiologic functions in hematopoiesis of Notch modified by O-fucose glycans, we examined mice with inducible inactivation of Pofut1 using Mx-Cre. These mice exhibited a reduction in T lymphopoiesis and in the production of marginal-zone B cells, in addition to myeloid hyperplasia. Restoration of Notch1 signaling rescued T lymphopoiesis and the marrow myeloid hyperplasia. After marrow transfer, both cell-autonomous and environmental cues were found to contribute to lymphoid developmental defects and myeloid hyperplasia in Pofut1-deleted mice. Although Pofut1 deficiency slightly decreased cell surface expression of Notch1 and Notch2, it completely abrogated the binding of Notch receptors with Delta-like Notch ligands and suppressed downstream Notch target activation, indicating that O-fucose glycans are critical for efficient Notch-ligand binding that transduce Notch signals. The combined data support a key role for the O-fucose glycans generated by Pofut1 in Notch regulation of hematopoietic homeostasis through modulation of Notch-ligand interactions.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cre recombinase,
http://linkedlifedata.com/resource/pubmed/chemical/Fucose,
http://linkedlifedata.com/resource/pubmed/chemical/Fucosyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/GDPmannose 4,6-dehydratase,
http://linkedlifedata.com/resource/pubmed/chemical/Hydro-Lyases,
http://linkedlifedata.com/resource/pubmed/chemical/Integrases,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Pofut1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Notch
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1528-0020
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pubmed:author |
pubmed-author:BøeH AHA,
pubmed-author:GersonStantonS,
pubmed-author:HuangXiaoranX,
pubmed-author:HuangYuanshuaiY,
pubmed-author:LoweJohn BJB,
pubmed-author:StanleyPamelaP,
pubmed-author:WangWeihuanW,
pubmed-author:WeiLebingL,
pubmed-author:YanQuanjianQ,
pubmed-author:YaoDavidD,
pubmed-author:ZhouLanL
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pubmed:issnType |
Electronic
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pubmed:day |
26
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5652-62
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pubmed:meshHeading |
pubmed-meshheading:21464368-Animals,
pubmed-meshheading:21464368-Bone Marrow Transplantation,
pubmed-meshheading:21464368-Cell Differentiation,
pubmed-meshheading:21464368-Cells, Cultured,
pubmed-meshheading:21464368-Flow Cytometry,
pubmed-meshheading:21464368-Fucose,
pubmed-meshheading:21464368-Fucosyltransferases,
pubmed-meshheading:21464368-Homeostasis,
pubmed-meshheading:21464368-Humans,
pubmed-meshheading:21464368-Hydro-Lyases,
pubmed-meshheading:21464368-Hyperplasia,
pubmed-meshheading:21464368-Integrases,
pubmed-meshheading:21464368-Ligands,
pubmed-meshheading:21464368-Lymphopoiesis,
pubmed-meshheading:21464368-Mice,
pubmed-meshheading:21464368-Mice, Knockout,
pubmed-meshheading:21464368-Mice, Transgenic,
pubmed-meshheading:21464368-Myelopoiesis,
pubmed-meshheading:21464368-RNA, Messenger,
pubmed-meshheading:21464368-Receptors, Notch,
pubmed-meshheading:21464368-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:21464368-Signal Transduction,
pubmed-meshheading:21464368-T-Lymphocytes
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pubmed:year |
2011
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pubmed:articleTitle |
Protein O-fucosyltransferase 1 (Pofut1) regulates lymphoid and myeloid homeostasis through modulation of Notch receptor ligand interactions.
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pubmed:affiliation |
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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