The phosphorylation of the Smad2/3 linker region by nemo-like kinase regulates TGF-β signaling.

ABSTRACT: Smad2 and Smad3 (Smad2/3) are structurally similar proteins that primarily mediate the transforming growth factor-β (TGF-β) signaling responsible for driving cell proliferation, differentiation, and migration. The dynamics of the Smad2/3 phosphorylation provide the key mechanism for regulating the TGF-β signaling pathway, but the details surrounding this phosphorylation remain unclear. Here, using in vitro kinase assay coupled with mass spectrometry, we identified for the first time that nemo-like kinase (NLK) regulates TGF-β signaling via modulation of Smad2/3 phosphorylation in the linker region. TGF-β-mediated transcriptional and cellular responses are suppressed by NLK overexpression, whereas NLK depletion exerts opposite effects. Specifically, we discovered that NLK associates with Sm

SUBMITTER: Liang J 

PROVIDER: S-EPMC8047224 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature