The Role of G Protein Methylation in the Function of a Geranylgeranylated 
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- 作者：Craig A. Parish ; Alan V. Smrcka ; and Robert R. Rando
- 刊名：Biochemistry
- 出版年：1996
- 出版时间：June 11, 1996
- 年：1996
- 卷：35
- 期：23
- 页码：7499 - 7505
- 全文大小：302K
- 年卷期：v.35,no.23(June 11, 1996)
- ISSN：1520-4995
文摘
The 
subunit of heterotrimeric G proteins isisoprenylated and methylated on its carboxylterminal cysteine residue. While retinal transducin isfarnesylated, all other subunits are modified bygeranylgeranylation. An immobilized form of pig liver esterase(iPLE) is able to hydrolyze the methylester of a geranylgeranylated 
isoform(12). Since methylation is the onlyreversible reaction in theisoprenylation pathway, it could be a site of regulation of G proteinactivity. With both the methylatedand demethylated 12 now available, therole of methylation for a geranylgeranylated heterotrimericGprotein may be addressed. Here, it is reported that methylationhas no effect on the ability of tointeract with an 
subunit, as probed by ADP-ribosylation studieswith pertussis toxin, and has a smalleffect (less than 2-fold) on the ability of geranylgeranylated to activate phosphatidylinositol-specificphospholipase C (PIPLC) and phosphoinositide 3 kinase (PI3K). Inbinding studies, demethylation onlyslightly decreased the ability of 12 toadhere to azolectin vesicles. Therefore, methylation ofheterotrimericG proteins appears to have only a minor effect in signal transductionprocesses which can be correlatedto a decrease in hydrophobicity of the subunit.
subunit of heterotrimeric G proteins isisoprenylated and methylated on its carboxylterminal cysteine residue. While retinal transducin isfarnesylated, all other subunits are modified bygeranylgeranylation. An immobilized form of pig liver esterase(iPLE) is able to hydrolyze the methylester of a geranylgeranylated isoform(12). Since methylation is the onlyreversible reaction in theisoprenylation pathway, it could be a site of regulation of G proteinactivity. With both the methylatedand demethylated 12 now available, therole of methylation for a geranylgeranylated heterotrimericGprotein may be addressed. Here, it is reported that methylationhas no effect on the ability of tointeract with an subunit, as probed by ADP-ribosylation studieswith pertussis toxin, and has a smalleffect (less than 2-fold) on the ability of geranylgeranylated to activate phosphatidylinositol-specificphospholipase C (PIPLC) and phosphoinositide 3 kinase (PI3K). Inbinding studies, demethylation onlyslightly decreased the ability of 12 toadhere to azolectin vesicles. Therefore, methylation ofheterotrimericG proteins appears to have only a minor effect in signal transductionprocesses which can be correlatedto a decrease in hydrophobicity of the subunit.