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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Commun 2017 ; 8 (ä): ä Nephropedia Template TP
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Engineered proteins with sensing and activating modules for automated reprogramming of cellular functions #MMPMID28883531
Sun J; Lei L; Tsai CM; Wang Y; Shi Y; Ouyang M; Lu S; Seong J; Kim TJ; Wang P; Huang M; Xu X; Nizet V; Chien S; Wang Y
Nat Commun 2017[]; 8 (ä): ä PMID28883531show ga
Protein-based biosensors or activators have been engineered to visualize molecular signals or manipulate cellular functions. Here we integrate these two functionalities into one protein molecule, an integrated sensing and activating protein (iSNAP). A prototype that can detect tyrosine phosphorylation and immediately activate auto-inhibited Shp2 phosphatase, Shp2-iSNAP, is designed through modular assembly. When Shp2-iSNAP is fused to the SIRP? receptor which typically transduces anti-phagocytic signals from the ?don?t eat me? CD47 ligand through negative Shp1 signaling, the engineered macrophages not only allow visualization of SIRP? phosphorylation upon CD47 engagement but also rewire the CD47-SIRP? axis into the positive Shp2 signaling, which enhances phagocytosis of opsonized tumor cells. A second SIRP? Syk-iSNAP with redesigned sensor and activator modules can likewise rewire the CD47-SIRP? axis to the pro-phagocytic Syk kinase activation. Thus, our approach can be extended to execute a broad range of sensing and automated reprogramming actions for directed therapeutics.