Zuo W, Chen YG#. Specific activation of MAPK by TGF-β receptors in lipid rafts is required for epithelial cell plasticity. MOLECULAR BIOLOGY OF THE CELL 20:1020-1029, 2009

Abstract Transforming growth factor (TGF)-beta regulates a spectrum of cellular events, including cell proliferation, differentiation, and migration. In addition to the canonical Smad pathway, TGF-beta can also activate mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and small GTPases in a cell-specific manner. Here, we report that cholesterol depletion interfered with TGF-beta-induced epithelial-mesenchymal transition (EMT) and cell migration. This interference is due to impaired activation of MAPK mediated by cholesterol-rich lipid rafts. Cholesterol-depleting agents specifically inhibited TGF-beta-induced activation of extracellular signal-regulated kinase (ERK) and p38, but not Smad2/3 or Akt. Activation of ERK or p38 is required for both TGF-beta-in......