Regulation of Translation by PKA Signaling Pathway

Extracellular stimuli, including hormones, growth factors and nutrients in the milieu of cells often initiate intracellular changes via signaling pathways, of which the cyclic 5', 3'-adnosine monophosphate (cAMP)-dependent protein kinase (PKA) signaling pathway is prototypical. Research in the past decades has demonstrated that PKA plays versatile roles during cell proliferation and differentiation, mainly through phosphorylating a plethora of protein substrates by its protein kinase activity. Studies using model systems including yeast, neurons and mammalian germ cells indicate that PKA functionality is regulated by not only the cell-type-specific expression of its regulatory and catalytic subunits, but also the spatiotemporal distribution of its binding proteins and secondary messengers. How PKA elicits its functional specificity in a spatiotemporal manner constitutes fundamental mechanisms that regulate development, aging and regeneration. In this review, we first summarize basic aspects that drive the functional diversity of PKA and then focus on the less studied regulatory roles of PKA during synthesis of cellular proteins, the functional units of the cell. Direct links between PKA signaling and protein synthesis machinery are yet to be fully characterized. We anticipate that research in this area, combining model systems and newly developed methodologies, will continue to deepen our understanding of animal development and the etiology of human diseases.