Functional Impacts of Signal Integration: Regulation of Inflammation-Related Transcription Factors by Heterotrimeric G Proteins

Oncogenic mutations of G proteins and G protein-coupled receptors (GPCRs) have been identified in various endocrine tumors for almost 20 years. Chronic inflammation contributes to tumorigenesis by the induction of cytokine and chemokine production and leukocyte infiltration. Many inflammatory mediators and chemoattractants elicit their effects by stimulating specific GPCRs. The subsequent activation of various G proteins often results in the modulation of transcription factors via complex signaling networks. Human herpesviruses can even resort to hijacking such control by making their own constitutive GPCRs that eventually lead to the development of Kaposi’s sarcoma. Increasing evidence indicates that inflammation-related transcription factors such as STAT3 and NFκB are common effectors of converging streams of G protein signals, which further signifies the importance of G protein-mediated regulations of inflammatory actions and tumorigenesis. This chapter aims to review the regulations of transcription factors mediated by G proteins and the biological relevance of cross-communications between different signaling cascades.