The experiences of a biochemist in the evolving world of G protein-dependent signaling.

This review describes how a biochemist and basic researcher (i.e. myself) came to make a career in the area of receptor-coupled signal transduction and the roles cellular signaling activities play both in normal physiology and in disease. Much of what has been the best part of this research life is due to the time I spent with Bob Lefkowitz (1982-1985), during an extraordinary period in the emerging field of G-protein-coupled receptors. Among my laboratory colleagues were some truly outstanding scientists including Marc Caron, the late Jeffrey Stadel, Berta Strulovici, Jeff Benovic, Brian Kobilka, and Henrik Dohlman, as well as many more. I came to Bob's laboratory after being trained as a physical biochemist and enzymologist. Bob and his laboratory exposed me to a research style that made it possible to connect the kinds of fundamental biochemical and mechanistic questions that I loved to think about with a direct relevance to disease. Indeed, I owe Bob a great deal for having imparted a research style and philosophy that has remained with me throughout my career. Below, I describe how this has taken me on an interesting journey through various areas of cellular signaling, which have a direct relevance to the actions of one or another type of G-protein.