Opposing effects of beta-arrestin1 and beta-arrestin2 on activation and degradation of Src induced by protease-activated receptor 1.
Protease-activated receptor 1 (PAR1), a G protein-coupled receptor for thrombin, is irreversibly proteolytically activated. beta-Arrestin1 and beta-arrestin2 have been reported to have different effects on signal desensitization and transduction of PAR1. In this study, we investigated whether beta-arrestin1 and beta-arrestin2 regulate Src-dependent activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) induced by PAR1 in HEK 293 cells. Our results show that PAR1-mediated activation of Src and ERK1/2 in HEK 293 cells was increased with overexpression of beta-arrestin1 or depletion of beta-arrestin2. PAR1-mediated activation of Src and ERK1/2 in HEK 293 cells was decreased or eliminated with depletion of beta-arrestin1 or overexpression of beta-arrestin2. Furthermore, depletion of beta-arrestin2 blocked PAR1-induced degradation of Src. Thus, beta-arrestin1 and beta-arrestin2 have opposing roles in regulating the activation of Src induced by PAR1. beta-Arrestin2 also appears to promote PAR1-induced degradation of Src. This degradation of Src provides a possible mechanism for terminating PAR1 signaling.
Institute of Molecular and Cellular Biology, Hsinchu 30013, Taiwan ROC.
Fang-Ting
FT
Kuo
Te-Ling
TL
Lu
Hua-Wen
HW
Fu
D019390:Arrestins / Q000145:classification* / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D044463:Receptor, PAR-1 / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D000071557:beta-Arrestins; D019061:src-Family Kinases / Q000187:drug effects / Q000378:metabolism*
D019390:Arrestins; D044463:Receptor, PAR-1; D000071557:beta-Arrestins; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases