Open AccessTGF-β ABROGATES TCR-MEDIATED SIGNALING BY UPREGULATING TYROSINE PHOSPHATASES IN T CELLS
Author(s) -
Mashkoor A. Choudhry,
Özcan Sir,
M. M. Sayeed
Publication year - 2001
Publication title -
shock
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/00024382-200115030-00006
Subject(s) - protein tyrosine phosphatase , tyrosine phosphorylation , phosphorylation , microbiology and biotechnology , tyrosine kinase , t cell , kinase , tyrosine , chemistry , phosphatase , signal transduction , receptor tyrosine kinase , biology , biochemistry , immune system , immunology
TGF-beta is known to inhibit many of the immune cell functions including T cell proliferation and IL-2 production. The mechanism of such TGF-beta-mediated inhibition of T cell functions is poorly understood. The present study examined the effects of TGF-beta on the activation of protein tyrosine kinases (PTK) P56lck, P59fyn, and Zap-70, and protein tyrosine phosphatases (PTP) SHP-1 and SHP-2. A balance between the actions of PTK and PTP is critical for appropriate T cell activation. These studies were carried out using nylon wool-purified splenic T cells from healthy Sprague-Dawley rats. Results from these studies showed that incubation of T cells with TGF-beta inhibited the activation of P56lck, P59fyn and Zap-70. The decrease in these three protein tyrosine kinases was accompanied by an increase in the activation of the protein tyrosine phosphatase SHP-1. There was no change in the phosphorylation of SHP-2 with and without pretreatment of T cells with TGF-beta. The decrease in P56lck, P59fyn kinase activity, and Zap-70 phosphorylation was prevented when T cells were stimulated with anti-CD3 in the presence of pervanadate, an inhibitor of PTP. These results suggested that TGF-beta-mediated inhibition of P56lck, P59fyn, and Zap-70 is likely due to an up-regulation of protein tyrosine phosphatases such as SHP-1.