Expression, signaling and function of Egr transcription factors in pancreatic β-cells and insulin-responsive tissues

• Egr proteins are zinc finger transcription factors.
• The activity of Egr transcription factors is controlled via the biosynthesis.
• Glucose, neurosteroids, and GPCR ligands upregulate EGR-1 expression and activity.
• Egr proteins regulate insulin biosynthesis, glucose homeostasis, and islet size.
• Egr-1 is an integral part of insulin receptor signaling.

Egr-1 and the related zinc finger transcription factors Egr-2, Egr-3, and Egr-4 are stimulated by many extracellular signaling molecules and represent a convergence point for intracellular signaling cascades. Egr-1 expression is induced in insulinoma cells and pancreatic β-cells following stimulation with either glucose, or pregnenolone sulfate. Moreover, stimulation of Gαq and Gαs-coupled receptors enhances EGR-1 gene transcription. Functional studies revealed that Egr transcription factors control insulin biosynthesis via regulation of Pdx-1 expression. Glucose homeostasis and pancreatic islet size are regulated by Egr transcription factors, indicating that these proteins control central physiological parameters regulated by pancreatic β-cells. In addition, Egr-1 is an integral part of the insulin receptor signaling cascade in insulin-responsive tissues and influences insulin resistance.