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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996
EISSN: 1596-9827
Vol. 14, No. 11, 2015, pp. 1969-1974
Bioline Code: pr15257
Full paper language: English
Document type: Research Article
Document available free of charge

Tropical Journal of Pharmaceutical Research, Vol. 14, No. 11, 2015, pp. 1969-1974

 en Cytotoxic T-lymphocyte Antigen-4 Binding to SHP2 Interacting Transmembrane Adapter Protein by Phosphorylation in T-Cell
Lee, Sung-Kyu & Kang, Hyun

Abstract

Purpose: To investigate potential cytotoxic T-lymphocyte antigen-4 (CTLA-4) binding partners and assess whether potential binding partners affect the full function of CTLA-4. .
Methods: The down-regulation effects of CTLA-4 and SIT were assessed by culturing CD3 stimulated T-cells. CTLA-4 and SIT proteins were measured by immunoblot analysis and production of interlukin-2 transcription activity evaluated by luciferase assay.
Results: CTLA-4 inhibited the interlukin-2 production capacity of CD3-stimulated T cells. CTLA-4 interaction with SHP2 interacting transmembrane adapter protein (SIT) in the down-regulation of the transcription of Interulin-2 required CTLA-4 binding to SIT tyrosine motifs. The SIT tyrosine mutants were significantly lower (25 – 75 %) after phosphorylation compared with WT-SIT (transfected cells, p < 0.05) and untreated control. The remaining 90 % phosphorylation in the F188ANS mutant can be explained by phosphorylation of other tyrosines in the sequence of SIT (p < 0.05). For interukin-2 transcription, F188ANS single mutant and double F148SEV mutant, increased NF-AT activity by 35 % compared with the wild type (p < 0.05).
Conclusion: The findings imply that SIT transmembrane adaptor (SIT) protein, binds to CTLA-4 and thus potentiates the inhibitory role of this co-receptor. This phenomenon may lead to the development of new treatment strategies for autoimmune diseases and graft rejection.

Keywords
Cytotoxic T-lymphocyte antigen-4; Interleukin-2; Nuclear factor of activated T-cells/Activator protein-1; SHP2 interacting transmembrane adapter protein; Autoimmune diseases; Graft rejection

 
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