PD‐1 inhibits T‐cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCθ

• DOI: 10.1016/j.febslet.2004.07.083
• Publication Date: 2004-08-17T13:09:01Z
• Authors: Kelly-Ann Sheppard; Lori J. Fitz; Julie M. Lee; Christina Benander; Judith A. George; Joe Wooters; Yongchang Qiu; Jason M. Jussif; Laura L. Carter; Clive R. Wood; Divya Chaudhary
• Keywords: Jurkat cells; ZAP70

Engagement of the immunoinhibitory receptor, programmed death‐1 (PD‐1) attenuates T‐cell receptor (TCR)‐mediated activation IL‐2 production and proliferation. Here, we demonstrate that PD‐1 modulation function involves inhibition TCR‐mediated phosphorylation ZAP70 association with CD3ζ. In addition, signaling PKCθ loop in a cognate TCR signal. has been shown to be required for production. A phosphorylated peptide, corresponding C‐terminal immunoreceptor tyrosine‐switch motif (ITSM), acts as docking site vitro both SHP‐2 SHP‐1, while peptide containing N‐terminal tyrosine based inhibitory (ITIM) associates only SHP‐2.