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Publication : The Notch regulator Numb links the Notch and TCR signaling pathways.

First Author  Anderson AC Year  2005
Journal  J Immunol Volume  174
Issue  2 Pages  890-7
PubMed ID  15634911 Mgi Jnum  J:95834
Mgi Id  MGI:3527382 Doi  10.4049/jimmunol.174.2.890
Citation  Anderson AC, et al. (2005) The Notch regulator numb links the Notch and TCR signaling pathways. J Immunol 174(2):890-7
abstractText  Both the Notch and TCR signaling pathways play an important role in T cell development, but the links between these signaling pathways are largely unexplored. The adapter protein Numb is a well-characterized inhibitor of Notch and also contains a phosphotyrosine binding domain, suggesting that Numb could provide a link between these pathways. We explored this possibility by investigating the physical interactions among Notch, Numb, and the TCR signaling apparatus and by examining the consequences of a Numb mutation on T cell development. We found that Notch and Numb cocluster with the TCR at the APC contact during Ag-driven T cell-APC interactions in both immature and mature T cells. Furthermore, Numb coimmunoprecipitates with components of the TCR signaling apparatus. Despite this association, T cell development and T cell activation occur normally in the absence of Numb, perhaps due to the expression of the related protein, Numblike. Together our data suggest that Notch and TCR signals may be integrated at the cell membrane, and that Numb may be an important adapter in this process.
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