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.
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References
Berridge, M. J. & Irvine, R. F. Nature 341, 197–205 (1989).
Nishizuka, Y. Nature 334, 661–665 (1988).
Meldrum, E., Parker, P. J. & Carozzi, A. Biochim. biophys. Acta 1092, 49–71 (1991).
Rhee, S. G. & Choi, K. D. Adv. Cyclic Nucleotide Prot. Phosph. Res. 26, 35–61 (1992).
De Vivo, M. & Gershengorn, M. C. in ADP-Ribosylating Toxins and G Proteins: Insights into Signal Transduction (eds Moss, J. & Vaughan, M.) 267–293 (American Society for Microbiology, Washington DC, 1990).
Birnbaumer, L., Abramowitz, J. & Brown, A. M. Biochim. biophys. Acta 1031, 163–224 (1990).
Taylor, S. J., Chae, H. Z., Rhee, S. G. & Exton, J. H. Nature 350, 516–518 (1991).
Smrcka, A. V., Hepler, J. R., Brown, K. O. & Sternweis, P. C. Science 251, 804–807 (1991).
Park, D. J., John, D.-Y., Kriz, R. W., Knopf, J. L. & Rhee, S. G. J. biol. Chem. 267, 16048–16055 (1992).
Lee, C. H., Park, D. J., Wu, D., Rhee, S. G. & Simon, M. I. J. biol. Chem. 267, 16044–16047 (1992).
Camps, M. et al. Eur. J. Biochem. 206, 821–831 (1992).
Tang, W.-J. & Gilman, A. G. Science 254, 1500–1503 (1991).
Gao, B. & Gilman, A. G. Proc. natn. Acad. Sci. U.S.A. 88, 10178–10182 (1991).
Federman, A. D., Conklin, B. R., Schrader, K. A., Reed, R. R. & Bourne, H. R. Nature 356, 159–161 (1992).
Jelsema, C. L. & Axelrod, J. Proc. natn. Acad. Sci. U.S.A. 84, 3623–3627 (1987).
Schmidt, C. J. & Neer, E. J. J. biol. Chem. 266, 4538–4533 (1991).
Gierschik, P., Sidiropoulos, D. & Jakobs, K. H. J. biol. Chem. 264, 21470–21473 (1989).
Van Sande, J. et al. Molec. cell. Endocrin. 74, R1–R6 (1990).
Guderman, T., Birnbaumer, M. & Birnbaumer, L. J. biol. Chem. 267, 4479–4488 (1992).
Chabre, O. et al. Molec. Endocrin. 6, 551–556 (1992).
Abou-Samra, A.-B. et al. Proc. natn. Acad. Sci. U.S.A. 89, 2732–2736 (1992).
Katan, M. et al. Cell 54, 171–177 (1988).
Kaufman, R. J. Meth. Enzym. 185, 487–511 (1990).
Gierschik, P., Codina, J., Simons, C., Birnbaumer, L. & Spiegel, A. M. Proc. natn. Acad. Sci. U.S.A. 82, 727–731 (1985).
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Camps, M., Carozzi, A., Schnabel, P. et al. Isozyme-selective stimulation of phospholipase C-β2 by G protein βγ-subunits. Nature 360, 684–686 (1992). https://doi.org/10.1038/360684a0
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DOI: https://doi.org/10.1038/360684a0
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