Lessons from viral hijacks of cells and cancer biology suggest that the activation of G protein-coupled receptors (GPCRs) often results in the modulation of various transcription factors and cofactors. Since drugs acting on GPCRs represent a significant portion of therapeutic agents currently in use, it is important to understand the actions of GPCRs on gene expression. GPCRs and their associated heterotrimeric G proteins are known to regulate gene transcription through complex signaling networks. The G protein-mediated signaling cascades have been extensively studied and accumulating evidence indicates that the four subfamilies of G proteins may utilize both common and unique pathways for transcriptional regulation. This review aims to provide a contemporary account of our understanding on the regulation of transcription factors by GPCRs, with a special emphasis on specific regulations of transcription factors such as STAT3 and NF-kappaB by individual G protein subfamilies. Functional impacts of the signal integration between different pathways and the contributions by other GPCR-interacting molecules will also be briefly discussed.

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