| E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity. | |
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MedLine Citation:
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PMID: 22763434 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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E3 ubiquitin ligase Cbl-b plays a crucial role in T cell activation and tolerance induction. However, the molecular mechanism by which Cbl-b inhibits T cell activation remains unclear. Here, we report that Cbl-b does not inhibit PI3K but rather suppresses TCR/CD28-induced inactivation of Pten. The elevated Akt activity in Cbl-b(-/-) T cells is therefore due to heightened Pten inactivation. Suppression of Pten inactivation in T cells by Cbl-b is achieved by impeding the association of Pten with Nedd4, which targets Pten K13 for K63-linked polyubiquitination. Consistent with this finding, introducing Nedd4 deficiency into Cbl-b(-/-) mice abrogates hyper-T cell responses caused by the loss of Cbl-b. Hence, our data demonstrate that Cbl-b inhibits T cell activation by suppressing Pten inactivation independently of its ubiquitin ligase activity. |
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Authors:
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Hui Guo; Guilin Qiao; Haiyan Ying; Zhenping Li; Yixia Zhao; Yanran Liang; Lifen Yang; Stanley Lipkowitz; Josef M Penninger; Wallace Y Langdon; Jian Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell reports Volume: 1 ISSN: 2211-1247 ISO Abbreviation: Cell Rep Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-09-24 Completed Date: 2013-04-17 Revised Date: 2013-05-16 |
Medline Journal Info:
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Nlm Unique ID: 101573691 Medline TA: Cell Rep Country: United States |
Other Details:
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Languages: eng Pagination: 472-82 Citation Subset: IM |
Affiliation:
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Section of Nephrology, Department of Medicine, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/BC032851; BC138813; NM008960 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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deficiency,
genetics,
metabolism* Animals Antigens, CD28 / metabolism Endosomal Sorting Complexes Required for Transport / deficiency, genetics, metabolism* Female Lymphocyte Activation / physiology Male Mice Mice, Inbred BALB C Mice, Knockout Models, Animal Molecular Sequence Data PTEN Phosphohydrolase / metabolism* Phosphatidylinositol 3-Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism Proto-Oncogene Proteins c-cbl / deficiency, genetics, metabolism* Receptors, Antigen, T-Cell / metabolism Signal Transduction / physiology T-Lymphocytes / metabolism*, pathology Ubiquitin-Protein Ligases / deficiency, genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AI090901/AI/NIAID NIH HHS; R01 AI090901/AI/NIAID NIH HHS; R01 AR049775/AR/NIAMS NIH HHS; R01AR049775/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Antigens, CD28; 0/Endosomal Sorting Complexes Required for Transport; 0/Receptors, Antigen, T-Cell; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.3.48/Pten protein, mouse; EC 3.1.3.67/PTEN Phosphohydrolase; EC 6.3.2.-/Proto-Oncogene Proteins c-cbl; EC 6.3.2.19/Cblb protein, mouse; EC 6.3.2.19/Nedd4 ubiquitin protein ligases; EC 6.3.2.19/Ubiquitin-Protein Ligases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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