I wanted to be a ballerina, but somehow, I ended up being a spectator and a student to the most intricate dance of all-that of an enzyme that performs center stage in the theater of cell signaling. Protein kinase C moves between cellular compart-ments, interacting with binding partners and second messengers, in an exquisitely choreographed dance of perfection and precision. The enzyme displays remarkable flexibility, undergoing global conformational changes as it pirouettes around the cell, from partner to partner. It is my prima ballerina assoluta and my favorite enzyme, all in one.
Dan Koshland, in an autobiographical article in Annual Reviews in Biochemistry (1) recounts that he felt like a character in the Mikado, ''wafted by a favoring gale'' from place to place. I too feel that the breezes were favorable as I was wafted from a B.Sc. in Biochemistry from Simon Fraser University in my hometown of Vancouver, to a Ph.D. in Chemistry at Stanford with Wray Huestis, and into the lab of Dan Koshland at the University of California, Berkeley for my postdoctoral studies. Koshland recruited me to solve memory. I succeeded Daria Mochly-Rosen, who was his first postdoctoral fellow to work on protein kinase C in his lab (1983)(1984)(1985). The enzyme had been discovered a few years earlier by Yasutomi Nishizuka and his group in Kobe, Japan (2). We overlapped for 1 month during which she provided me with intense and rigorous training in protein kinase C-memorable for the 5 day-long, round the clock, purifications of protein kinase C (imagine, no tags!) from rat brain; I will not forget the day a decapitated rat head bit my glove to the music of the Talking Heads. As Daria recounts in an article on his life we wrote together for this journal (3), Koshland had decided that protein kinase C was the memory enzyme because repetitive painting on mouse skin of phorbol esters, which had just been shown to activate protein kinase C, caused cancer. Reasoning there was a mechanism to ''remember'' the previous application, he charged me with solving memory mediated by protein kinase C.
For the first two weeks in the Koshland lab, I diligently set forth to develop a system to repetitively stimulate protein kinase C in cells and study desensitization, the closest I could think of to memory. I was getting nowhere quickly. After I had been in the lab about a week, Koshland asked if had solved memory yet. I replied that yes, I had, but I had forgotten the answer. After two weeks, it stopped being funny. So, I secretly started looking at the lipid regulation of protein kinase C. My graduate training was in lipid biochemistry, something much more tangible than memory. By then it was well known from Nishizuka's discoveries that protein kinase C was activated by lipids and