1 I suspected that this enzyme might be placing a phosphate on the 3 position of the inositol ring to produce phosphatidylinsitol-3-phosphate (PI-3-P), but I realized that this would be heretical to the field and would require rigorous chemical proof, since PI-3-P had not been previously described.
So, at the Cold Spring Harbor meeting I sought out Bob Michel and Peter Downes, two of the most experienced biochemists in this field, and told them of our findings. While both were skeptical that a novel phosphoinositide had been missed after more than 35 years of research in this field, they both offered advice about how to prove the structure and Downes agreed to collaborate in this endeavor. With Downes' help, we were able to unambiguously define the structure and thereby reveal a new phosphatidylinositol 3-kinase (PI3K) signaling pathway.2 Its significance, however, remained unclear.
The 1980s were an exciting ...
