articleScienceApr 8, 2016GREEN OA

Phase separation of signaling molecules promotes T cell receptor signal transduction

Marine Biological Laboratory · Howard Hughes Medical Institute · +3 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Activation of various cell surface receptors triggers the reorganization of downstream signaling molecules into micrometer- or submicrometer-sized clusters. However, the functional consequences of such clustering have been unclear. We biochemically reconstituted a 12-component signaling pathway on model membranes, beginning with T cell receptor (TCR) activation and ending with actin assembly. When TCR phosphorylation was triggered, downstream signaling proteins spontaneously separated into liquid-like clusters that promoted signaling outputs both in vitro and in human Jurkat T cells. Reconstituted clusters were enriched in kinases but excluded phosphatases and enhanced actin filament assembly by recruiting and…

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