Endocytosis-dependent lysosomal degradation of Src induced by protease-activated receptor 1

Chung Che Tsai, Fang Ting Kuo, Sung Bau Lee, Yu Ting Chang, Hua Wen Fu

研究成果: 雜誌貢獻文章


Src plays a critical role in regulating cellular responses induced by protease-activated receptor 1 (PAR1). Here, we found that PAR1 activation induces lysosomal degradation of Src. Src is associated and trafficked together with activated PAR1 to early endosomes and then sorted to lysosomes for degradation. Blocking agonist-induced endocytosis of PAR1 by inhibition of dynamin activity suppresses PAR1-induced degradation of Src. However, Src activity is neither required for agonist-induced PAR1 internalization nor required for Src degradation upon PAR1 activation. We show that PAR1 activation triggers endocytosis-dependent lysosomal degradation of Src in both human embryonic kidney 293 and human umbilical vein endothelial cells. Our finding provides a new paradigm for how an irreversibly activated receptor regulates its downstream signalling.
頁(從 - 到)504-517
期刊FEBS Letters
出版狀態已發佈 - 三月 1 2019


ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology