A protein tyrosine phosphatase inhibitor, pervanadate, inhibits angiotensin II-Induced beta-arrestin cleavage.
Beta-arrestins turn off G protein-mediated signals and initiate distinct G protein-independent signaling pathways. We previously demonstrated that angiotensin AT(1) receptor-bound 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.
Jang
Sei-Heon
SH
Department of Molecular Biology, Daegu University, Gyeongsan 712-714, Korea.
Hwang
Si Ae
SA
Kim
Mijin
M
Yun
Sung-Hae
SH
Kim
Moon-Sook
MS
Karnik
Sadashiva S
SS
Lee
ChangWoo
C
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D019390:Arrestins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D008982:Molybdenum / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011487:Protein Conformation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
C000605256:Arrb1 protein, rat; D019390:Arrestins; D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; C076715:pervanadate; D000804:Angiotensin II; C044659:molybdate; D049452:Green Fluorescent Proteins; D014638:Vanadates; D014443:Tyrosine; D008982:Molybdenum; D017027:Protein Tyrosine Phosphatases