FIG. 9.

G protein-dependent and G protein-independent signaling activities of M33. Use of pharmacological and genetic inhibitors at multiple steps along the G_q/11 signaling pathway reveals that CREB activation by the MCMV GPCR M33 is mediated by coupling to heterotrimeric G_q/11 proteins and PLC-β activity. Moreover, while not affected by IP₃ and Ca²⁺ levels, CREB activity is dependent on PKC activity and is augmented by increased levels of DAG. Conversely, M33 stimulation of p38 (which may partially contribute to M33-induced CREB activity) and NF-κB occurs in the absence of G_q/11 signaling through an as-yet-defined mechanism(s).