Novel bimodal effects of the G-protein tissue transglutaminase on adrenoreceptor signalling

Tissue transglutaminase (tTG) is a novel G-protein that previous studies showed can couple ligand-bound activated α_1B adrenoreceptors to phospholipase C-δ, resulting in phosphoinositide (PI) hydrolysis. In human neuroblastoma SH-SY5Y cells we found that although endogenous tTG can facilitate α_1B adrenoreceptor-stimulated PI hydrolysis, its contribution is minor compared with the classical heterotrimeric G-protein G_q/11. Further, we show that the α_1B adrenoreceptor recruits tTG to the membrane and that this recruitment is enhanced by agonist occupancy of the receptor. In addition, the effects of tTG on signalling are bimodal. At low expression levels, tTG enhanced α_1B adrenoreceptor-stimulated PI hydrolysis, whereas at higher expression levels tTG attenuated significantly this response. These findings are the first to demonstrate that a protein can both facilitate and attenuate receptor-stimulated PI hydrolysis.