A novel adaptor protein, STAP-2 functions as a signal modulator in immune system

Abstract

Signal-transducing adaptor protein-2 (STAP-2) was recently identified as a novel adaptor protein and is a family of STAP adaptor protein and has a variety of functions in cellular signal transductions. Especially STAP-2 has a crucial role in immune systems by controlling cytokine signal transduction. STAP-2 functionally interacts with STAT3 through its YXXQ motif and enhances STAT3 transcriptional activation. In contrast, STAP-2 interacts with STAT5 through its PH and SH2-like domains and decreases STAT5 activity. Importantly, STAP-2 also binds to MyD88 and IKK-α/β and regulates LPS/TLR4 signaling. Moreover, STAP-2 interacts with Epstein-Barr virus-derived LMP1 and modulates LMP1-mediated NF-κB signaling. More importantly, experiments using STAP-2 deficient mice showed that STAP-2 modulated several T-cell functions. T-cells from STAP-2 deficient mice showed enhanced integrin-mediated cell adhesion to fibronectin. Furthermore STAP-2-deficient T-cells show reduced chemotaxis toward SDF-1α. These accumulated evidences indicate that novel adaptor protein STAP-2 plays an important modulator role in both of innate and adaptive immune systems. © 2010 The Pharmaceutical Society of Japan.