SMAD2 S-palmitoylation promotes its linker region phosphorylation and T_H17 cell differentiation in a mouse model of multiple sclerosis.

ABSTRACT: The transcriptional regulators SMAD2 and SMAD3 share the same primary signaling pathway in response to the cytokine TGFβ. However, whereas SMAD2 stimulates the differentiation of naive CD4⁺ T cells into proinflammatory T helper 17 cells (T_H17 cells), SMAD3 stimulates the differentiation of anti-inflammatory regulatory T cells (T_reg cells). Here, we report a dynamic SMAD2-specific posttranslational modification important for T_H17 cell differentiation. SMAD2, but not SMAD3, was reversibly S-palmitoylated at cysteine-41 and cysteine-81 by the palmitoyltransferase DHHC7 and depalmitoylated by the acyl protein thioesterase APT2. As a result, SMAD2 was recruited to intracellular membranes where its linker region was phosphorylated, leading to its inter

SUBMITTER: Zhang M 

PROVIDER: S-EPMC12234153 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature