Yasutomi Nishizuka

news and views Obituary hypothesized that it could be linked with PIP2 metabolism. Yasutomi Nishizuka (1932–2004) Nishizuka made another breakthrough in 1982, following an inspiring encounter Ever since the discovery of hormones at with Monique Castagna, who visited the beginning of the last century, the Kobe from Paris. Castagna’s interest was cellular responses to these molecules have the tumour-promoting properties of been high on the research agenda for phorbol esters, and the outcome of her biologists. During the 1970s and 1980s, collaboration with Nishizuka was the answers began to emerge at the molecular finding that these compounds activate level, most notably through the protein kinase C continuously, thus identification of key molecules and events causing uncontrolled cell growth. that follow the binding of a hormone to Born into a medical family, Nishizuka receptors on the cell surface, and transfer had followed the lead of his older brother the hormonal signal to the cell nucleus to Yasuaki, a well-known pathologist, elicit a response. choosing to become a biochemist after So it was that terms and processes that studying medicine. Nishizuka began are now textbook material were unveiled. his scientific career in 1958 as the first The activation of G proteins, which are graduate student of Osamu Hayaishi associated with hormone receptors inside in the Department of Medical Chemistry the cell, leads to the activation of protein at Kyoto University. Hayaishi had just kinase A. Activated G proteins can also returned to Japan from the US National trigger the metabolism of phospholipids Institutes of Health. At the time, Japanese in the cell membrane, particularly cleavage biochemistry was dominated by of phosphatidylinositol-4,5-bisphosphate chemistry-oriented research, mostly aimed (PIP2) into inositol-1,4,5-trisphosphate at identifying new chemical compounds in (IP3) and diacylglycerol, a molecule that metabolites, but Hayaishi introduced the in turn activates protein kinase C. The practice of studying processes and activated protein kinases A and C reactions rather than just end products. phosphorylate other proteins, initiating Consequently, Nishizuka had a thorough a cascade of phosphorylations that hand Discoverer of key grounding in enzymology, and the the activation signal from one protein to protein activation importance of considering the the next until it reaches the nucleus and pathways physiological function of molecules stimulates the correct response. was imprinted on his science. Yasutomi Nishizuka, who died on widely recognized, except for the As a scientist, Nishizuka was very 4 November, was one of the main figures conservation of bioenergy in the high- critical when considering data — I in this biological revolution. In 1989, he energy phosphate discovered by Lipmann, remember him as always being the last was a co-winner of the Lasker award for the and the control of glycolysis by the person to be convinced by new results. But discovery of protein kinase C, along with phosphorylation of key proteins elucidated he was otherwise warm-hearted and gentle, Michael Berridge for the identification by Edmond Fischer and Krebs. So when with a sense of humour. He revered the of IP3 function, Alfred Gilman for the Nishizuka returned to Kyoto University arts, particularly music (he played the discovery of G proteins and their function, in 1965, he started work on an enzyme piano) and painting. His artistic sense was and Edwin Krebs for his pioneering work that phosphorylated other proteins, which evident in his lecture slides — quite an on protein phosphorylation. Gilman and later turned out to be protein kinase A. achievement, because for much of his career Krebs later received the Nobel prize for In January 1969, Nishizuka was each letter had to be stencilled by hand. their contributions. appointed professor of biochemistry at On 17 January 1995, a huge earthquake Nishizuka became interested in protein Kobe University School of Medicine. His struck Kobe, destroying several of the phosphorylation when he visited the new lab had belonged to the Department of university buildings — and damaging Rockefeller University in New York in 1964 Industrial Medicine, and he was surprised Nishizuka’s home. Only two weeks after and 1965 to work with Fritz Lipmann on to find the space occupied by bicycles and this disaster, Nishizuka was named how proteins are synthesized. During his a large bathtub, with no biochemical president of Kobe University, and in the stay, he purified proteins called elongation equipment or lab benches. He wasted ensuing six years of his term of office he factors G and T, which aid the growth of no time in setting up the lab, however, and rebuilt the university and re-established the amino-acid chain, and elucidated the attracted several brilliant medical students it as a competitive academic institution. role of GTP in the process. to join him as postgraduates. The team At the time of his death he was serving Nishizuka’s time with Lipmann and began studying calcium-dependent as president of Hyogo Prefectural his colleagues was comparatively brief, protein phosphorylation. Nishizuka Centre for Adult Disease and on many but it gave him a strong impetus to work originally thought that a calcium- government advisory committees. He will on the biological function of heavily dependent protease triggered the be remembered as a great and charismatic phosphorylated nuclear proteins. kinase activity in brain cell extracts, but scientist. Tasuku Honjo Lipmann had himself studied it soon became clear that the membrane Tasuku Honjo is in the Department of Medical phosphorylated proteins in the 1930s, phospholipid fraction was responsible, Chemistry and Molecular Biology, when he was a visiting scientist at the and the activator turned out to be Kyoto University Faculty of Medicine, Rockefeller. But even in the 1960s, the diacylglycerol. Nishizuka coined the name Kyoto 6068501, Japan. regulatory roles of phosphate were not protein kinase C for this kinase, and he e-mail: [email protected] 966 NATURE | VOL 432 | 23/30 DECEMBER 2004 | www.nature.com/nature © 2004 Nature Publishing Group.

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