A genetic library screen for signaling proteins that interact with phosphorylated T cell costimulatory receptors Journal Article
| Authors: | Zang, X.; Loke, P.; Kim, J.; Wojnoonski, K.; Kusdra, L.; Allison, J. P. |
| Article Title: | A genetic library screen for signaling proteins that interact with phosphorylated T cell costimulatory receptors |
| Abstract: | 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. © 2006 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; nonhuman; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; gene; protein protein interaction; protein; gene library; phosphorylation; phosphatidylinositol 3 kinase; mice, transgenic; t lymphocyte receptor; lymphocyte activation; receptors, antigen, t-cell; nucleotide sequence; 1-phosphatidylinositol 3-kinase; cell stimulation; genetic screening; functional genomics; t lymphocytes; two-hybrid system techniques; phosphatidylinositol 3-kinase; costimulation; antigens, differentiation, t-lymphocyte; protein p85; inducible costimulator; hybrid; dna library; icos gene |
| Journal Title: | Genomics |
| Volume: | 88 |
| Issue: | 6 |
| ISSN: | 0888-7543 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2006-12-01 |
| Start Page: | 841 |
| End Page: | 845 |
| Language: | English |
| DOI: | 10.1016/j.ygeno.2006.08.012 |
| PUBMED: | 17014982 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 4 June 2012" - "CODEN: GNMCE" - "Molecular Sequence Numbers: GENBANK: AAQ20845, AAX46485, BAA82128, CAB71153, CAC06612, XP_421959;" - "Source: Scopus" |
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