Nishizuka obtained his MD (1957) and PhD (1962) from Kyoto University, and — except for a year at Rockefeller University with Nobel laureate Fritz Lipmann — remained there until 1969. His work during that period included studies on the biosynthesis of nicotinamide adenine dinucleotide (NAD), the involvement of GTP in ribosomal protein translation and ADP-ribosylation by diphtheria toxin. In 1969 he became professor and head of the Department of Biochemistry at Kobe University, where he established an outstanding research group focused on the roles of protein kinases in signal transduction.
When he and his colleagues identified a novel protein kinase that required membrane phospholipids and Ca2+ ions, and dubbed it protein kinase C (PKC; Takai et al. J. Biol. Chem. 252, 7603–7609; 1977 and Takai et al. J. Biol. Chem. 254, 3692–3695; 1979), this was the start of a sequence of remarkable results. They found that 'contaminants' in the initial phospholipid samples were needed for PKC activation: a 'trace' of unsaturated 1,2-diacylglycerol was the key. This evoked a most improbable insight: the activating diacylglycerol — to most of us, a common and fairly boring lipid — might be a novel second messenger generated by receptor-stimulated phosphoinositide hydrolysis (Takai, Y. et al. Biochem. Biophys. Res. Commun. 91, 1218–1224; 1979).
