TGFβR2

TGFβR2 is the type II TGF-β receptor that initiates signaling after ligand binding and activates TGFβR1/ALK5, which then drives SMAD2/3 transcriptional responses^[1]. Mechanistically, TGFβR2 expression levels tune SMAD and MAPK-ERK activation, linking receptor abundance to pathway specificity, p21 induction, and TGF-β-mediated apoptosis^[2]. Compared with related TGF-β isoforms, TGF-β2 binds TβRII weakly and depends more on betaglycan, whereas residue differences explain stronger receptor binding by TGF-β1 and TGF-β3^[3]. In colorectal cancer, TGFBR2 mononucleotide mutations occur frequently in MSI-high tumors but do not add prognostic value beyond MSI status^[4]. In mouse intestinal tumors, epithelial Tgfbr2 loss cooperates with Apc mutation to promote invasion and malignant transformation^[5]. For experimental applications, CRISPR/Cas9 TGFBR2 knockout in CAR T cells or ovarian cancer TILs reduces TGF-β immunosuppression and improves antitumor function in TGF-β-rich models^[6][7]. A soluble splice variant, TβRII-SE, binds all three TGF-β isoforms and supports fibrosis-model testing of ligand-sequestration strategies^[8].- TGFβR2 connects ligand recognition to SMAD2/3 signaling and context-dependent MAPK-ERK activation^[1][2]. - TGFBR2 mutation and knockout models support colorectal cancer and immunotherapy mechanism studies^[4][5][6][7]. - Isoform-selective binding distinguishes TGF-β2 biology and guides receptor-focused experimental design^[3][8].