From the Glucose Metabolism to the Signal Transduction Study

- ATP, Sphingosine 1-phosphate, and Protons -

Abstract

This review article summarizes my work as a researcher over the past 40 years. I began my life as a researcher at Hokkaido University as a graduate student, and remained there, first as a post-doctoral fellow and later as a research associate, until 1987. My major discovery during this period was that the GTP binding protein was involved in not only the adenylyl cyclase coupling receptor system, but also the Ca²⁺ mobilizing hormone receptor system. I later moved to Gunma University and investigated, first as an associate professor and later as a professor, the role of ATP, sphingosine 1-phosphate (S1), and protons as extracellular signaling ligands of GTP binding protein-coupled receptors. Although our group was not the first to discover that the proton is a signaling ligand, ATP and S1P had not been recognized as signaling molecules at the time of my initial investigations. The discovery that SIP mediates anti-atherogenic actions of high-density lipoprotein is internationally recognized. On the other hand, research on the proton is still relatively new, and many topics remain unsolved.