Phosphoinositide-binding activity of Smad2 is essential for its function in TGF-β signaling.

ABSTRACT: As a central player in the canonical TGF-β signaling pathway, Smad2 transmits the activation of TGF-β receptors at the plasma membrane (PM) to transcriptional regulation in the nucleus. Although it has been well established that binding of TGF-β to its receptors leads to the recruitment and activation of Smad2, the spatiotemporal mechanism by which Smad2 is recruited to the activated TGF-β receptor complex and activated is not fully understood. Here we show that Smad2 selectively and tightly binds phosphatidylinositol-4,5-bisphosphate (PI(4,5)P₂) in the PM. The PI(4,5)P₂-binding site is located in the MH2 domain that is involved in interaction with the TGF-β receptor I that transduces TGF-β-receptor binding to downstream signaling proteins. Quantitative optical imagin

SUBMITTER: Buwaneka P 

PROVIDER: S-EPMC8567202 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature