A novel GPI-anchored dominant-negative TGF-β receptor II renders T cells unresponsive to TGF-β signaling.

ABSTRACT: Transforming growth factor β (TGF-β) is a pleiotropic cytokine expressed by a wide range of cell types and is known for hampering the effectiveness of cancer immune cell therapeutic approaches. We have designed a novel construct containing the extracellular domain of the TGF-β receptor II linked to a glycosylphosphatidylinositol (GPI) anchor (GPI-ecto-TβRII) lacking the transmembrane and cytoplasmic signaling domain of TGF-β receptor II (TβRII). T cells transduced with lentivirus expressing the GPI-ecto-TβRII construct show 5 to 15 times higher membrane expression compared with a previously established dominant-negative receptor carrying a truncated signaling domain. GPI-ecto-TβRII expression renders T cells unresponsive to TGF-β-induced signaling seen by a lack of SMAD phosphorylation upo

SUBMITTER: Petersen SH 

PROVIDER: S-EPMC10565558 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature