Journal
SHOCK
Volume 15, Issue 3, Pages 193-199Publisher
BIOMEDICAL PRESS
DOI: 10.1097/00024382-200115030-00006
Keywords
T lymphocytes; anti-CD3; sodium pervanadate; signal transduction; P56(lck); P59(fyn); Zap-70; SHP-1; SHP-2; inflammatory mediators
Funding
- NIGMS NIH HHS [R01GM56865, R01GM53235] Funding Source: Medline
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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) P56(lck), P59(fyn), 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 P56(lck), P59(fyn), 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 P56(lck), P59(fyn) kinase activity, and Zap-70 phosphorylation was prevented when T cells were stimulated with anti-CDS in the presence of pervanadate, an inhibitor of PTP. These results suggested that TGF-beta -mediated inhibition of P56(lck), P59(fyn), and Zap-70 is likely due to an up-regulation of protein tyrosine phosphatases such as SHP-1.
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