| γ-Secretase-regulated signaling pathways, such as notch signaling, mediate the differentiation of hematopoietic stem cells, development of the immune system, and peripheral immune responses. | |
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MedLine Citation:
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PMID: 21190540 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Notch signaling mediates the fates of numerous cells in both invertebrates and vertebrates. In the immune system, Notch signalling contributes to the generation of hematopoietic stem cells (HSCs), the promotion of HSC self-renewal, T lineage commitment, intrathymic T cell development, and peripheral lymphocyte differentiation/activation. The intracellular domain (ICD) of Notch is released from the cell membrane by γ-secretase and translocates to the nucleus to modulate gene expression. Hence, γ-secretase plays a central role in the regulation of Notch signaling. More than five dozen type 1 transmembrane proteins, including amyloid precursor protein, Notch, and Delta, are substrates for γ-secretase and their ICDs are released from the cell membrane. Therefore, it is highly possible that mechanisms similar to Notch signaling may widely contribute to γ-secretase-regulated signaling. Besides Notch, some transmembrane proteins such as CD44 and CSF-1R, which are important for immune responses, have been reported as substrates for γ-secretase. Since the ICDs of these proteins are also released by γ-secretase from the cell membrane and localize to the nucleus, it is thought that these ICDs modulate gene expression. Thus, γ-secretase-regulated signaling, including Notch signaling, may play a wide range of roles in the immune system. |
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Authors:
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Hisashi Nagase; Chang-Sung Koh; Kohzo Nakayama |
Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Current stem cell research & therapy Volume: 6 ISSN: 1574-888X ISO Abbreviation: Curr Stem Cell Res Ther Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-02 Completed Date: 2011-09-27 Revised Date: 2012-01-19 |
Medline Journal Info:
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Nlm Unique ID: 101272517 Medline TA: Curr Stem Cell Res Ther Country: United Arab Emirates |
Other Details:
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Languages: eng Pagination: 131-41 Citation Subset: IM |
Affiliation:
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Department of Immunology and Infectious Diseases, Shinshu University, School of Medicine, Matsumoto, Nagano 390-8621, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amyloid Precursor Protein Secretases
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metabolism* Animals Cell Differentiation* Hematopoietic Stem Cells / cytology* Humans Immune System / physiology* Peripheral Nerves / immunology* Receptors, Notch / metabolism* Signal Transduction* |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Notch; EC 3.4.-/Amyloid Precursor Protein Secretases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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