Cross Talk between Protein Kinase A and Androgen Signaling Pathway

Abstract

Protein kinases are enzymes that add phosphate group to proteins to modify their function. These proteins regulate signal transduction pathways, essential for many biological processes such as cell cycle, cell signaling, protein and enzyme regulation, etc. There are 518 protein kinases, divided in to 7 main families. Protein kinase A (PKA) is a member of AGC family of protein kinases. It is activated by activation of G protein-coupled receptors (GPCR) and plays an important role in many cellular pathways including androgen signaling. Steroid hormones such as androgens primarily function through a genomic pathway, binding to cytosolic androgen receptors (AR) and initiating changes in transcription of target genes. Androgens also functions through a non-genomic pathway which is rapid and mediated by membrane receptors. It manifests its effects by activation of cellular signal transduction pathways such as PKA, Protein kinase C, and mitogen activated kinase, and does not involve transcription. In this review, we have analyzed the interaction between androgen signaling pathways and PKA, and have highlighted how each of these pathways complements and strengthens the function of the other. PKA plays an important role in complete activation of nuclear AR and in turn PKA can be activated by androgens. The complex interaction between the two pathways plays a critical role in development and progression of prostate cancer (PCa). Though the exact role of each pathway is not completely understood yet simultaneous inhibition of both pathways could prove to be beneficial for PCa patients.