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Publication : A genetic library screen for signaling proteins that interact with phosphorylated T cell costimulatory receptors.

First Author  Zang X Year  2006
Journal  Genomics Volume  88
Issue  6 Pages  841-845
PubMed ID  17014982 Mgi Jnum  J:121867
Mgi Id  MGI:3712417 Doi  10.1016/j.ygeno.2006.08.012
Citation  Zang X, et al. (2006) A genetic library screen for signaling proteins that interact with phosphorylated T cell costimulatory receptors. Genomics 88(6):841-5
abstractText  In the past decade, the fundamental importance and therapeutic potential of costimulatory signals for lymphocyte activation have spurred a large amount of work in immunology, infection, cancer, autoimmune diseases, etc. However, the mechanisms behind T cell costimulation remain unclear, partly due to the lack of suitable techniques. There is an urgent need for functional genomic research to develop comprehensive approaches to direct identification of protein-protein interactions that are dependent on the posttranslational modification of one component of the complex, particularly in the field of T cell immunology. Using inducible costimulator (ICOS) as a model, we failed to find any proteins that associated with the cytoplasmic tail of ICOS by the yeast two-hybrid approach. Therefore, we have developed a new yeast three-hybrid system that facilitates the rapid screening of cDNA libraries to find signaling molecules that interact with phosphorylated T cell costimulatory receptors. We demonstrate the utility of this technique to detect the interaction between ICOS and the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K). The p85 unit of PI3K is the only signaling molecule identified so far that interacts with ICOS. This system may be of great help in dissecting the mechanisms of T cell costimulation and could be applied to other receptors.
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