Cytotoxic T lymphocyte antigen 4 (CTLA-4) interferes with extracellular signal-regulated kinase (ERK) and Jun NH sub(2)-terminal kinase (JNK) activation, but does not affect phosphorylation of T cell receptor zeta and ZAP70

• Published in: The Journal of experimental medicine Vol. 186; no. 10; pp. 1645 - 1653
• Main Authors: Calvo, C R, Amsen, D, Kruisbeek, A M
• Format: Journal Article
• Language: English
• Published: 01.12.1997
• ISSN: 0022-1007

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an important regulator of T cell homeostasis. Ligation of this receptor leads to prominent downregulation of T cell proliferation, mainly as a consequence of interference with IL-2 production. We here report that CTLA-4 engagement strikingly selectively shuts off activation of downstream T cell receptor (TCR)/CD28 signaling events, i.e., activation of the microtubule-associated protein kinase (MAPKs) ERK and JNK. In sharp contrast, proximal TCR signaling events such as ZAP70 and TCR- zeta chain phosphorylation are not affected by CTLA-4 engagement on activated T cells. Since activation of the ERK and JNK kinases is required for stimulation of interleukin (IL)-2 transcription, these data provide a molecular explanation for the block in IL-2 production imposed by CTLA-4.