Regulation of intracellular cAMP by multiple pathways enables differential function of this ubiquitous second messenger in a context-dependent manner. Modulation of Gs-stimulated intracellular cAMP has long been known to be modulated by the Gi and Gq/Ca2+ pathways. Recently, the G13 pathway was also shown to facilitate cAMP responses in murine macrophage cells. We report here that this synergistic regulation of cAMP synthesis by the Gs and G13 pathways is mediated by a specific isoform of adenylyl cyclase, AC7. Furthermore, this signaling paradigm exists in several hematopoietic lineages and can be recapitulated by exogenous expression of AC7 in HEK 293 cells. Mechanistic characterization of this synergistic interaction indicates that it occurs downstream of receptor activation and it can be mediated by the α subunit of either G 12 or G13. Our results demonstrate that AC7 is a specific downstream effector of the G12-13 pathway.
|Original language||English (US)|
|Number of pages||11|
|Journal||Journal of Biological Chemistry|
|State||Published - Aug 22 2008|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology