Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-08-01

AUTHORS

M-C Fargnoli, RL Edelson, CL Berger, S Chimenti, C Couture, T Mustelin, R Halaban

ABSTRACT

Malignant cells of patients with cutaneous T cell lymphoma (CTCL) are of monoclonal origin and of the CD4+/CD45RO+ subset. Since unlike their normal counterparts, triggering of their TCR/CD3 in vitro elicits only a weak mitogenic response, we set out to determine which of the signal transduction molecules initiated by anti-CD3ε antibodies are affected in neoplastic cells. The results obtained from analysis of tumor cells from four patients show a general reduction in basal and induced tyrosine phosphorylation of a wide range of signaling proteins. Furthermore, the function of members from distinct families of protein tyrosine kinases was altered in neoplastic cells. The enzymatic activity of the membrane-bound fraction of Csk was suppressed, and its association with other cellular proteins was altered. There was a decline in the amount and activity of Syk, and a slight decrease in the specific activity of Lck kinases. Zap70 tyrosyl phosphorylation was reduced or undetectable and the kinase associated weakly, or not at all, with the TCR ζ chain. We propose that dampened TCR-triggered responses in CTCL are caused by suppression of an array of effector molecules required for coupling cell surface receptors to early and late signaling events. More... »

PAGES

1338-1346

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.leu.2400745

DOI

http://dx.doi.org/10.1038/sj.leu.2400745

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041185834

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/9264390


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