FUNCTIONAL-SIGNIFICANCE OF BETA-GAMMA-SUBUNIT CARBOXYMETHYLATION FOR THE ACTIVATION OF PHOSPHOLIPASE-C AND PHOSPHOINOSITIDE 3-KINASE

被引:56
作者
PARISH, CA
SMRCKA, AV
RANDO, RR
机构
[1] HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115
[2] UNIV ROCHESTER,DEPT PHARMACOL,ROCHESTER,NY 14642
关键词
D O I
10.1021/bi00023a019
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
The gamma subunits of heterotrimeric G proteins are isoprenylated and methylated at their carboxyl-terminal cysteine residues. Since methylation is the only reversible reaction in the isoprenylation pathway, it could be a site of regulation of G protein activity. beta subunits have been shown to activate a number of effecters involved in signal transduction pathways. The methyl group of retinal transducin (T) can be hydrolyzed by an immobilized form of pig liver esterase, allowing for a direct determination of the activities of methylated and demethylated T-beta gamma. The abilities of methylated and demethylated T-beta gamma to stimulate G protein regulated phosphatidylinositol-specific phospholipase C (PIPLC) and phosphoinositide 3-kinase (PI3K) were determined. It is reported here that there is a strong dependence on methylation for activating both PIPLC and PI3K. Demethylated T-beta gamma is at least 10-fold less active than its methylated counterpart. Therefore, methylation may play an important role in the regulation of these effecters and of signal transduction processes in general.
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收藏
页码:7722 / 7727
页数:6
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