Gbeta 5gamma 2 is a highly selective activator of phospholipid-dependent enzymes.

Udo Maier, Aleksei Babich, Nathalie Macrez, Daniela Leopoldt, Peter Gierschik, Daria Illenberger, Bernd Nürnberg
Journal of Biological Chemistry. 2000-05-01; 275(18): 13746-13754
DOI: 10.1074/jbc.275.18.13746

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1. J Biol Chem. 2000 May 5;275(18):13746-54.

Gbeta 5gamma 2 is a highly selective activator of phospholipid-dependent enzymes.

Maier U(1), Babich A, Macrez N, Leopoldt D, Gierschik P, Illenberger D, Nurnberg
B.

Author information:
(1)Institut für Pharmakologie, Freie Universität Berlin, Thielallee 69-73, 14195
Berlin (Dahlem), Germany.

In this study, Gbeta specificity in the regulation of Gbetagamma-sensitive
phosphoinositide 3-kinases (PI3Ks) and phospholipase Cbeta (PLCbeta) isozymes was
examined. Recombinant mammalian Gbeta(1-3)gamma(2) complexes purified from Sf9
membranes stimulated PI3Kgamma lipid kinase activity with similar potency (10-30
nm) and efficacy, whereas transducin Gbetagamma was less potent. Functionally
active Gbeta(5)gamma(2) dimers were purified from Sf9 cell membranes following
coexpression of Gbeta(5) and Ggamma(2-His). This preparation as well as
Gbeta(1)gamma(2-His) supported pertussis toxin-mediated ADP-ribosylation of
Galpha(i1). Gbeta(1)gamma(2-His) stimulated PI3Kgamma lipid and protein kinase
activities at nanomolar concentrations, whereas Gbeta(5)gamma(2-His) had no
effect. Accordingly, Gbeta(1)gamma(2-His), but not Gbeta(5)gamma(2-His),
significantly stimulated the lipid kinase activity of PI3Kbeta in the presence or
absence of tyrosine-phosphorylated peptides derived from the p85-binding domain
of the platelet derived-growth factor receptor. Conversely, both preparations
were able to stimulate PLCbeta(2) and PLCbeta(1). However, Gbeta(1)gamma(2-His),
but not Gbeta(5)gamma(2-His), activated PLCbeta(3). Experimental evidence
suggests that the mechanism of Gbeta(5)-dependent effector selectivity may differ
between PI3K and PLCbeta. In conclusion, these data indicate that Gbeta subunits
are able to discriminate among effectors independently of Galpha due to selective
protein-protein interaction.

DOI: 10.1074/jbc.275.18.13746
PMID: 10788495 [Indexed for MEDLINE]

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