Inhibitors of clathrin-dependent endocytosis enhance TGFβ signaling and responses

Chun Lin Chen, Wei Hsien Hou, I. Hua Liu, George Hsiao, Shuan Shian Huang, Jung San Huang

研究成果: 雜誌貢獻文章

90 引文 斯高帕斯(Scopus)

摘要

Clathrin-dependent endocytosis is believed to be involved in TGFβ-stimulated cellular responses, but the subcellular locus at which TGFβ induces signaling remains unclear. Here, we demonstrate that inhibitors of clathrin-dependent endocytosis, which are known to arrest the progression of endocytosis at coated-pit stages, inhibit internalization of cell-surface-bound TGFβ and promote colocalization and accumulation of TβR-I and SARA at the plasma membrane. These inhibitors enhance TGFβ-induced signaling and cellular responses (Smad2 phosphorylation/nuclear localization and expression of PAI-1). Dynasore, a newly identified inhibitor of dynamin GTPase activity, is one of the most potent inhibitors among those tested and, furthermore, is a potent enhancer of TGFβ. Dynasore ameliorates atherosclerosis in the aortic endothelium of hypercholesterolemic ApoE-null mice by counteracting the suppressed TGFβ responsiveness caused by the hypercholesterolemia, presumably acting through its effect on TGFβ endocytosis and signaling in vascular cells.
原文英語
頁(從 - 到)1863-1871
頁數9
期刊Journal of Cell Science
122
發行號11
DOIs
出版狀態已發佈 - 六月 1 2009

ASJC Scopus subject areas

  • Cell Biology

指紋 深入研究「Inhibitors of clathrin-dependent endocytosis enhance TGFβ signaling and responses」主題。共同形成了獨特的指紋。

  • 引用此