Role of the gamma subunit prenyl moiety in G protein beta gamma complex interaction with phospholipase C beta

The G protein beta gamma complex regulates a wide range of effectors, inclu ding the phospholipase C beta isozymes (PLC betas). Prenyl modification of the gamma subunit is necessary for this activity. Evidence presented here s upports a direct interaction between the G protein gamma subunit prenyl gro up and PLC isozymes. A geranylgeranylated peptide corresponding to the C-te rminal region of the gamma subunit type, gamma2, strongly inhibits stimulat ion of PLC beta2 and PLC beta3 activity by the beta gamma complex. This eff ect is specific because the same peptide has no effect on stimulation of PL C beta by an a subunit type, alphaq. Prenylation of the gamma peptide is re quired for its inhibitory effect. W interaction of prenylated gamma subunit peptide to fluophore-tagged PLC beta2 was examined by fluorescence spectro scopy, prenylated but not unprenylated peptide increased PLC beta2 fluoresc ence emission energy, indic ting direct binding of the prenyl moiety to PLC . In addition, fluorescence resonance energy transfer was detected between fluorophore tagged PLC beta and wild type Py complex but not an unprenylate d mutant beta gamma complex. We conclude that a major function of the gamma subunit prenyl group is to facilitate direct protein-protein interaction b etween the beta gamma complex and an effector, phospholipase C beta.