Yoshito Kaziro (April 18, 1929 – June 29, 2011) was a Japanese biochemical and medical scientist who performed research on the effects and mechanisms of ATP and GTP driven conformational changes in enzymes and intracellular signaling pathways for over 50 years.
[2] Over the course of Kaziro's career, he served as a researcher, mentor, and professor while always expressing a warm personality to his peers and students.
[3] Kaziro took an International Postdoctoral Fellowship opportunity from the U.S. Public Health Service that brought him to conduct research with Professor Severo Ochoa at the Department of Biochemistry at New York University Medical Center.
[1] Kaziro and Ochoa studied the mechanism of carbon dioxide fixation involved with the carboxylation of CoA proteins for three years.
[2][3] Kaziro and Ochoa’s research proposed the steps of a mechanism for the propionyl carboxylase reaction involving the exchange of ATP and ADP.
[3] In April 1990, Kaziro joined the DNAX Research Institute of Molecular and Cellular Biology and was appointed as the counseling professor of the Department of Chemistry at Stanford University in Palo Alto, California.
[1] In 1993, Kaziro returned to Japan and founded a new laboratory at the Faculty of Bioscience and Biotechnology called the Tokyo Institute of Technology (TIT).
[1] During his time at the TIT, Kaziro conducted research on the differential display of mRNA which came to be a well-known technique used to identify which genes use G protein signaling to regulate their activation.
[8] Additionally, Kaziro conducted research on a human homologue of apoptosis-associated tyrosine kinase (AATYK) and identified isoforms that are novel Cdk5/p35-bnding proteins involved with the cell cycle progression.
[9] In April 2000, Kaziro retired from the TIT and became the Vice President of Sanyo Gakuen University, located in his birth town of Okayama, Japan.
Additionally, Kaziro assisted in proposing a mechanism for the carboxylation of CoA proteins resulting from a conformational change induced by ATP hydrolysis.
[11] By producing a crystallized pig heart propionyl carboxylase, Kaziro and his team were able to observe the effects of biotin and sulfhydryl binding reagents on the enzyme’s function.
[12] The research team proposed an overall mechanism involving the exchange of ATP for ADP and Pi resulting in the attachment of CO2 to the propionyl carboxylase enzyme.
[5] The researchers found that 5’-guanylylmethylenediphosphonate (Gpp(CH2)p), a nonhydrolyzable form for GTP, could be used to study the reaction’s impact on Complex II of the ribosome.
[14] By establishing a human squamous carcinoma cell line, Kaziro and his team were able to produce large quantities of purified G-CSF.
[6] Kaziro also characterized the promoter region of the human Gs alpha gene as having an extremely high guanine nucleotide content.
[6] In 1991, Kaziro compiled years of his research involving the structure and function of GTP binding proteins and described various signal transduction pathways.
[15] Additionally, Kaziro studied a particular mutation of G-protein coupled inward rectifiers (GIRKs) that may play a role in the development of Andersen’s disease.
[16] The research team concluded that the area of the mutation must be one of the determinants for controlling the ion gate opening for GIRKs and potassium inward rectifier channels.