Biochemical and Biophysical Research Communications, Vol.490, No.2, 574-579, 2017
Binding of coronin 1B to T beta RI negatively regulates the TGF beta 1 signaling pathway
Coronin 1B is an actin-binding protein that regulates several actin-dependent cellular processes including migration and endocytosis. However, the role of coronin 1B in the tumor growth factor (TGF)beta signaling pathway is largely unknown. Here, we investigated whether coronin 1B affects the TGF beta signaling cascade and found that coronin 1B negatively regulates the TGF beta signaling pathway. Immunoprecipitation and glutathione-S-transferase-pulldown assays revealed that coronin 1B directly associated with TGF receptor I (T beta RI). Overexpression of coronin 1B inhibited the TGF beta 1-induced interaction between T beta RI and Smad2/3 in plasmid-transfected HEK293T cells. Coronin 1B was basally bound to T beta RI in vascular smooth muscle cells (VSMCs), but TGF beta 1 stimulation did not affect their association, suggesting constitutive binding between coronin 1B and T beta RI. Overexpression of coronin 1B suppressed TGF beta 1-induced activation of a Smad-binding element-luciferase reporter construct and a plasminogen activator inhibitor (PAI)-1 promoter-luciferase reporter construct in HEK293T cells. By contrast, depletion of coronin 1B by siRNA transfection increased TGF beta 1-induced Smad2/3 phosphorylation and PAI-1 expression in VSMCs. These results suggest that coronin 1B regulates the TGF beta 1 signaling cascade by constitutively interacting with T beta RI and inhibiting the binding of Smad2/3 to T beta RI in response to TGF beta 1 stimulation. (C) 2017 Elsevier Inc. All rights reserved.