A Protein Tyrosine Phosphatase Inhibitor, Pervanadate, Inhibits Angiotensin II-Induced β-Arrestin Cleavage

  • Jang, Sei-Heon (Department of Molecular Biology, Daegu University) ;
  • Hwang, Si Ae (Department of Molecular Biology, Daegu University) ;
  • Kim, Mijin (Department of Molecular Biology, Daegu University) ;
  • Yun, Sung-Hae (Daegu Science High School) ;
  • Kim, Moon-Sook (Daegu Science High School) ;
  • Karnik, Sadashiva S. (Department of Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic Foundation) ;
  • Lee, ChangWoo (Department of Molecular Biology, Daegu University)
  • Received : 2009.03.08
  • Accepted : 2009.06.09
  • Published : 2009.07.31


${\beta}$-Arrestins turn off G protein-mediated signals and initiate distinct G protein-independent signaling pathways. We previously demonstrated that angiotensin $AT_1$ receptorbound ${\beta}$-arrestin 1 is cleaved after $Phe^{388}$ upon angiotensin II stimulation. The mechanism and signaling pathway of angiotensin II-induced ${\beta}$-arrestin cleavage remain largely unknown. Here, we show that protein Tyr phosphatase activity is involved in the regulation of ${\beta}$-arrestin 1 cleavage. Tagging of green fluorescent protein (GFP) either to the N-terminus or C-terminus of ${\beta}$-arrestin 1 induced conformational changes and the cleavage of ${\beta}$-arrestin 1 without angiotensin $AT_1$ receptor activation. Orthovanadate and molybdate, inhibitors of protein Tyr phosphatase, attenuated the cleavage of C-terminal GFP-tagged ${\beta}$-arrestin 1 in vitro. The inhibitory effects of okadaic acid and pyrophosphate, which are inhibitors of protein Ser/Thr phosphatase, were less than those of protein Tyr phosphatase inhibitors. Cell-permeable pervanadate inhibited angiotensin II-induced cleavage of ${\beta}$-arrestin 1 in COS-1 cells. Our findings suggest that Tyr phosphorylation signaling is involved in the regulation of angiotensin II-induced ${\beta}$-arrestin cleavage.


Supported by : Daegu University, Korea Science and Engineering Foundation


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