Isozyme-selective stimulation of phospholipase C-β2 by G protein βγ-subunits

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Abstract
HYDROLYSIS by phospholipase C (PLC) of phosphatidylinositol 4,5-bisphosphate is a key mechanism by which many extracellular signalling molecules regulate functions of their target cells1,2. At least eight distinct isozymes of PLC are recognized in mammalian cells3,4. Receptor-controlled PLC is often regulated by G proteins, which can be modified by pertussis toxin in some cells but not in others5 6. In the latter cells, PLC-β1, but not PLC-γl or PLC-δ1, may be activated by members of the αq-subfamily of the G protein α-subunits7–10. An unidentified PLC in soluble fractions of cultured human HL-60 granulocytes is specifically stimulated by G protein βγ subunits purified from retina and brain11. Identification of a second PLC-β complementary DNA (PLC-β2) in an HL-60 cell cDNA library9 prompted us to investigate the effect of purified G protein βγ subunits on the activities of PLC-β1 and PLC-β2 transiently expressed in cultured mammalian cells. We report here that PLC-β1 and PLC-β2 were stimulated by free βγ subunits and that PLC-β2 was the most sensitive to βγ stimulation. Thus stimulation of PLC by βγ subunits is isozyme-selective and PLC-β2 is a prime target of βγ stimulation. Activation of PLC-β2 by βγ subunits may be an important mechanism by which pertussis toxin-sensitive G proteins stimulate PLC.