Endocytosis‐dependent lysosomal degradation of Src induced by protease‐activated receptor 1
2019
Tsai, Chung‐Che | Kuo, Fang‐Ting | Lee, Sung‐Bau | Chang, Yu‐Ting | Fu, Hua‐Wen
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.
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