The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway.

摘要: T cell activation by antigens binding to the receptor (TCR) must be properly regulated ensure normal development and effective immune responses pathogens transformed cells while avoiding autoimmunity. The Src family kinase Lck Syk ZAP-70 (ζ chain-associated protein of 70 kD) are sequentially activated in response TCR engagement serve as critical components signaling machinery that leads activation. We performed a mass spectrometry-based phosphoproteomic study comparing quantitative differences temporal dynamics phosphorylation stimulated unstimulated with or without inhibition catalytic activity. data indicated activity stimulates negative feedback pathways target thereby modulate patterns immunoreceptor tyrosine-based motifs (ITAMs) CD3 ζ chain molecules downstream Lck, including ZAP-70. developed computational model provides mechanistic explanation for experimental findings on ITAM wild-type cells, ZAP-70-deficient inhibited This incorporated regulation predicted order which tyrosines ITAMs chains phosphorylated consistent data.