PHORBOL-ESTER-INDUCED PHOSPHORYLATION OF THE BETA-2-ADRENERGIC RECEPTOR DECREASES ITS COUPLING TO GS

被引：55

作者：

BOUVIER, M ^{[1
]}

GUILBAULT, N ^{[1
]}

BONIN, H ^{[1
]}

机构：

[1] UNIV MONTREAL,RECH SYST NERVEUX AUTONOME GRP,MONTREAL H3C 3J7,QUEBEC,CANADA

来源：

FEBS LETTERS | 1991年 / 279卷 / 02期

关键词：

BETA-2-ADRENERGIC RECEPTOR; PHOSPHORYLATION; PROTEIN KINASE-C; ADENYLYL CYCLASE; DESENSITIZATION; PHORBOL-ESTER; RECEPTOR UNCOUPLING;

D O I：

10.1016/0014-5793(91)80159-Z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Phorbol-esters have been shown to modulate the beta-adrenergic-stimulated adenylyl cyclase in a number of cell lines. Here, using site directed mutagenesis, we investigate the role of the beta-2-adrenergic receptor phosphorylation by protein kinase C in this regulatory process. Mutation of the serine-261, -262, -344 and -345 of the beta-2-adrenergic receptor prevented the phorbol-ester-induced phosphorylation of the receptor. This mutation also abolished the phorbol-ester-induced decrease in high-affinity agonist binding and potency of the beta-2-adrenergic receptor. We suggest that protein kinase C mediated phosphorylation of the receptor promotes its functional uncoupling.

引用

页码：243 / 248

页数：6

共 39 条

[1]

BELL JD, 1985, J BIOL CHEM, V260, P2625

[2]

BOUVIER M, 1987, J BIOL CHEM, V262, P3106

[3]

BOUVIER M, 1987, MOL PHARMACOL, V33, P133

[4]

BOUVIER M, 1990, ANN NY ACAD SCI, V564, P120

[5]

BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3

[6]

BROSTROM MA, 1982, J BIOL CHEM, V257, P6758

[7]

CLARK RB, 1989, MOL PHARMACOL, V36, P343

[8] ACTIVATION OF CAMP-DEPENDENT PROTEIN-KINASE IS REQUIRED FOR HETEROLOGOUS DESENSITIZATION OF ADENYLYL CYCLASE IN S49 WILD-TYPE LYMPHOMA-CELLS [J].

CLARK, RB ;

KUNKEL, MW ;

FRIEDMAN, J ;

GOKA, TJ ;

JOHNSON, JA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (05) :1442-1446

[9] TUMOR PROMOTERS ENHANCE BASAL AND GROWTH-HORMONE RELEASING-FACTOR STIMULATED CYCLIC-AMP LEVELS IN ANTERIOR-PITUITARY CELLS [J].

CRONIN, MJ ;

CANONICO, PL .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1985, 129 (02) :404-410

[10]

CULLEN BR, 1987, METHOD ENZYMOL, V152, P684

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