Document Detail


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.
MedLine Citation:
PMID:  21190540     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Hisashi Nagase; Chang-Sung Koh; Kohzo Nakayama
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current stem cell research & therapy     Volume:  6     ISSN:  1574-888X     ISO Abbreviation:  Curr Stem Cell Res Ther     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-09-27     Revised Date:  2012-01-19    
Medline Journal Info:
Nlm Unique ID:  101272517     Medline TA:  Curr Stem Cell Res Ther     Country:  United Arab Emirates    
Other Details:
Languages:  eng     Pagination:  131-41     Citation Subset:  IM    
Affiliation:
Department of Immunology and Infectious Diseases, Shinshu University, School of Medicine, Matsumoto, Nagano 390-8621, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amyloid Precursor Protein Secretases / metabolism*
Animals
Cell Differentiation*
Hematopoietic Stem Cells / cytology*
Humans
Immune System / physiology*
Peripheral Nerves / immunology*
Receptors, Notch / metabolism*
Signal Transduction*
Chemical
Reg. No./Substance:
0/Receptors, Notch; EC 3.4.-/Amyloid Precursor Protein Secretases

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