Tissue transglutaminase (tTG) is a novel G-protein that previous studies sh
owed can couple ligand-bound activated alpha(1B) adrenoreceptors to phospho
lipase C-delta, resulting in phosphoinositide (PI) hydrolysis. In human neu
roblastoma SH-SY5Y cells we found that although endogenous tTG can facilita
te alpha(1B) adrenoreceptor-stimulated PI hydrolysis, its contribution is m
inor compared with the classical heterotrimeric G-protein G(q/11). Further,
we show that the alpha(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 alpha(1B) adrenoreceptor-stimulated PI hydrolysis, whe
reas at higher expression levels tTG attenuated significantly this response
. These findings are the first to demonstrate that a protein can both facil
itate and attenuate receptor-stimulated PI hydrolysis.