Signal transduction in atria and ventricles of mice with transient cardiacexpression of activated G protein alpha q

We recently showed that the transient expression of a hemagglutinin (HA) ep itope-tagged, constitutively active mutant of the G protein alpha(q) subuni t (HA alpha(q)*) in the hearts of transgenic mice is sufficient to induce c ardiac hypertrophy and dilatation that continue to progress after HA alpha( q)* protein becomes undetectable. We demonstrated that the activity of phos pholipase C beta, the immediate downstream target of activated G alpha(q), is increased at 2 weeks, when HA alpha(q)* is expressed, but also at 10 wee ks, when HA alpha(q)* is no longer detectable. This observation suggested t hat the transient HA alpha(q)* expression causes multiple, persistent chang es in cellular signaling pathways. We now demonstrate changes in the level, activity, or both of several signaling components, including changes in th e amount and hormone responsiveness of phospholipase C beta enzymes, in the basal level of diacylglycerol (which predominantly reflects activation of phospholipase D), in the amount or distribution of protein kinase C (PKC) i soforms (PKC alpha, PKC delta, and PKC epsilon), and in the amount of sever al endogenous G proteins. These changes vary depending on the isoform of th e signaling molecule, the chamber in which it is expressed, and the presenc e or absence of HA alpha(q)*. Our results suggest that a network of linked signaling functions determines the development of hypertrophy. They also su ggest that atria and ventricles represent different signaling domains. It i s likely that such changes occur in other model systems in which the activi ty of a single signaling component is increased, either due to an activatin g mutation or due to overexpression of the wild type.