Home
Resources
Publications
Intracellular Cytoplasm-Specific Delivery of SH3 and SH2 Domains of SLAP Inhibits TcR-mediated Signaling

Intracellular Cytoplasm-Specific Delivery of SH3 and SH2 Domains of SLAP Inhibits TcR-mediated Signaling

Jung-Ho Kim, Jae-Seung Moon, JiSang Yu, Sang-Kyou Lee

Biochem Biophys Res Commun. 2015 May 8;460(3):603-8.

PMID: 25800872

Abstract:

Signaling events triggered by T cell receptor (TcR) stimulation are important targets for the development of common therapeutics for various autoimmune diseases. SLAP is a negative regulator of TcR-mediated signaling cascade via targeting TcR zeta chain for degradation through recruiting the ubiquitin ligase c-Cbl. In this study, we generated a transducible form of SH3 and SH2 domains of SLAP (ctSLAPΔC) which can be specifically targeted to the cytoplasm of a cell. ctSLAPΔC inhibited tyrosine phosphorylation of signaling mediators such as ZAP-70 and LAT involved in T cell activation, and effectively suppressed transcriptional activity of NFAT and NFκB upon TcR stimulation. The transduced ctSLAPΔC in T cells blocked the secretion of T cell-specific cytokines such as IL-2, IFNγ, IL-17A, and IL-4 and induced the expression of CD69 and CD25 on effector T cells without influencing the cell viability. Inhibition of TcR-mediated signaling via SLAP blocked the differentiation of naïve T cells into Th1, Th2 or Treg cells with different sensitivity, suggesting that qualitative and quantitative intensity of TcR-mediated signaling in the context of polarizing cytokines environment may be a critical factor to determine the differentiation fate of naïve T cells. These results suggest that cytoplasm-specific transduction of the SH3 and SH2 domains of SLAP has a therapeutic potential of being an immunosuppressive reagent for the treatment of various autoimmune diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS7932283	SLAP N-Bn-3Me-Pip Reagent			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: