The untapped potential of tyrosine-based G protein signaling.

Tyrosine-based and trimeric G protein-based signaling are the two most widely studied and distinct mechanisms for signal transduction in eukaryotes. How each of them relay signals across the plasma membrane independently of each other has been extensively characterized; however, an understanding of how they work together remained obscure. Recently, a rapidly emerging paradigm has revealed that tyrosine based signals are relayed via G proteins, and that the cross-talk between the two hubs are more robustly and sophisticatedly integrated than was previously imagined. More importantly, by straddling the two signaling hubs that are most frequently targeted for their therapeutic significance, the tyrosine-based G-protein signaling pathway has its own growing list of pathophysiologic importance, both as therapeutic target in a variety of disease states, and by paving the way for personalized medicine. The fundamental principles of this emerging paradigm and its pharmacologic potential are discussed.