Refining minimal engineered receptors for specific activation of on-target signaling molecules.

ABSTRACT: Since designer cells are attracting much attention as a new modality in gene and cell therapy, it would be advantageous to develop synthetic receptors that recognize artificial ligands and activate solely signaling molecules of interest. In this study, we refined the construction of our previously developed minimal engineered receptors (MERs) to avoid off-target activation of STAT5 while maintaining on-target activation of signaling molecules corresponding to tyrosine motifs. Among the myristoylated, cytoplasmic, and transmembrane types of MERs, the cytoplasmic type had the highest signaling efficiency, although there was off-target activation of STAT5 upon ligand stimulation. Tyrosine-to-phenylalanine ​​mutagenesis revealed that both the tyrosine motif for recruiting target signaling mole

SUBMITTER: Miura M 

PROVIDER: S-EPMC11685922 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature