Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Cytotoxic T-lymphocyte antigen-4 binding to SHP2 interacting transmembrane adapter protein by phosphorylation in T-cell

Sung-Kyu Lee, Hyun Kang

Department of Medical Laboratory Science, College of Health Science, Dankook University, Cheonan-si, Chungnam, 330-714, Republic of Korea;

For correspondence:-

Received: 9 July 2015 Accepted: 11 October 2015 Published: 29 November 2015

Citation: Lee S, Kang H. Cytotoxic T-lymphocyte antigen-4 binding to SHP2 interacting transmembrane adapter protein by phosphorylation in T-cell. Trop J Pharm Res 2015; 14(11):1969-1974 doi: 10.4314/tjpr.v14i11.3

© 2015 The authors.
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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 prote