Chapter 7 - Bringing the Signal into the Nucleus: Regulation of Gene Expression

Abstract

This chapter is about transcription and how it is regulated by protein kinase A (PKA) and its substrate cAMP response element-binding protein (CREB) in the context of glucagon-driven gluconeogenesis. The chapter elaborates on PKA, its synthesis, posttranslational modifications, structure and function, the phosphosite sequences of its substrates, and how cAMP causes its activation. It shows the structure of the regulatory subunit (PRKAR), its association with the protein kinase and with anchor proteins (AKAPs), and how these contribute to the formation and subcellular location of signaling complexes. The chapter then switches to a brief overview of gene transcription, transcription factors, the transcription initiation complex, and the role of histone acetylation and methylation in rendering DNA accessible. This is followed by a brief description of the glucagon-signaling pathway, and a detailed description of how CREB recruits histone-acetyltransferases, CRTC2, the SWI/SNF-, promoter-core, and mediator complex. The chapter concludes by explaining how CREB brings about, in cooperation with nuclear receptors, expression of enzymes that control gluconeogenesis.