摘要
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.
原文 | 英語 |
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頁(從 - 到) | 504-517 |
頁數 | 14 |
期刊 | FEBS Letters |
卷 | 593 |
發行號 | 5 |
DOIs | |
出版狀態 | 已發佈 - 3月 1 2019 |
ASJC Scopus subject areas
- 生物物理學
- 結構生物學
- 生物化學
- 分子生物學
- 遺傳學
- 細胞生物學