title: Functional significance of beta gamma-subunit carboxymethylation for the activation of phospholipase C and phosphoinositide 3-kinase.
abstract: 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 gamma subunits have been shown to activate a number of effectors 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 effectors and of signal transduction processes in general.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Parish
authors.forename: A V
authors.initials: AV
authors.lastname: Smrcka
authors.forename: R R
authors.initials: RR
authors.lastname: Rando
mesh_terms: D000818:Animals; D002417:Cattle; D004789:Enzyme Activation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D066298:In Vitro Techniques; D008745:Methylation; D008823:Micelles; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry; D015398:Signal Transduction; D015293:Transducin / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D008823:Micelles; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D012243:Rhodopsin; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D010738:Type C Phospholipases; D015293:Transducin