Stimulation of Phospholipase C by G-Protein βγ Subunits

Abstract

The hydrolysis by phospholipase C of phosphatidylinositol 4,5-bisphosphate (PtdInsP₂) to inositol 1,4,5-trisphosphate (InsP₃) and diacylglycerol is a key mechanism by which many extracellular signaling molecules (e.g., hormones, growth factors, and neurotransmitters) regulate functions of their target cells (Berridge and Irvine 1989; Nishizuka 1988). There is ample evidence to suggest that many of the receptors interacting with these mediators stimulate phospholipase C via a guanine nucleotide binding protein (G-protein) (Cockcroft and Stutchfield 1988; De Vivo and Gershengorn 1990). In certain cell types, e.g., neutrophils and cultured granulocytes like HL-60 cells (Ohta et al. 1985; Krause et al. 1985), mast cells (Nakamura and Ui 1985), or renal mesangial cells (Pfeilschifter and Bauer 1986), the relevant G-protein appears to be a substrate for ADP-ribosylation by pertussis toxin. In other cells, e.g., cultured chick heart cells (Masters et al. 1985), 1321N1 astrocytoma cells (Hepler and Harden 1986), GH₃ pituitary cells (Martin et al. 1986), or hepatocytes (Uhing et al. 1986) stimulation of phospholipase C is mediated by G-protein(s) resistant to modification by pertussis toxin. Recently, evidence has been presented suggesting that, in the latter systems, PLCβ₁, but not PLCγ₁ or PLGδ₁, is activated by members of the newly discovered α_q subfamily of the G-protein α subunits (see Chaps. 58 and 67 by Exton and Park, this volume, for review and references). With regard to stimulation of phospholipase C by pertussis-toxin-sensitive G-proteins, however, little information has been available until recently on the nature the G-protein involved.