Members of the G Protein-Coupled Receptor Kinase Family That Phosphorylate the 2-Adrenergic Receptor Facil

详细信息    查看全文

• 作者：Luc Mé ; nard ; Stephen S. G. Ferguson ; Larry S. Barak ; Lucie Bertrand ; Richard T. Premont ; Anne-Marie Colapietro ; Robert J. Lefkowitz ; and Marc G. Caron
• 刊名：Biochemistry
• 出版年：1996
• 出版时间：April 2, 1996
• 年：1996
• 卷：35
• 期：13
• 页码：4155 - 4160
• 全文大小：274K
• 年卷期：v.35,no.13(April 2, 1996)
• ISSN：1520-4995

文摘

We recently reported that a SRC="/images/gifchars/beta2.gif" BORDER=0 ALIGN="middle">₂-adrenergic receptor(s/gifchars/beta2.gif" BORDER=0 ALIGN="middle">₂AR) mutant, Y326A, defective in itsability to sequester in response to agonist stimulation was a poorsubstrate for G protein-coupled receptorkinase (GRK)-mediated phosphorylation; however, its ability to bephosphorylated and sequestered couldbe restored by overexpressing GRK2 [Ferguson etal. (1995) J. Biol. Chem.270, 24782]. In the presentreport, we tested the ability of each of the known GRKs (GRK1-6) tophosphorylate and rescue thesequestration of the Y326A mutant in HEK-293 cells. We demonstratethat in addition to GRK2, GRK3-6can phosphorylate the Y326A mutant and rescue its sequestration;however, GRK1 was totally ineffectivein rescuing either the phosphorylation or the sequestration of themutant receptor. We found that theagonist-dependent rescue of Y326A mutant phosphorylation by GRK2, -3,and -5 was associated withthe agonist-dependent rescue of sequestration. In contrast,overexpression of GRK4 and -6 led mainly toagonist-independent phosphorylation of the Y326A mutant accompanied byincreased basal receptorsequestration. Our results demonstrate that phosphorylationper se, but not the interaction with aspecificGRK, is required to facilitate s/gifchars/beta2.gif" BORDER=0 ALIGN="middle">₂ARsequestration.