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.
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology
- Cell Biology
Tsai, C. C., Kuo, F. T., Lee, S. B., Chang, Y. T., & Fu, H. W. (2019). Endocytosis-dependent lysosomal degradation of Src induced by protease-activated receptor 1. FEBS Letters, 593(5), 504-517. https://doi.org/10.1002/1873-3468.13336