Structural requirement of leucine for activation of p70 S6 kinase

The addition of leucine induced activation of p70(S6k) in amino acid-depleted H4IIE cells. Whereas the activation of p70(S6k) by leucine was transient, the complete amino acid stimulated p70(S6k) more persistently. The effect of leucine on p70(S6k) was sensitive to rapamycin, but less sensitive to wortmannin. Using various amino acids and derivatives of leucine, we found that the chirality, the structure of the four branched hydrocarbons, and the primary amine are required for the ability of leucine to stimulate p70(S6k), indicating that the structural requirement of leucine to induce p70(S6k) activation is very strict and precise. In addition, some leucine derivatives exhibited the ability to stimulate p70(S6k) and the other derivatives acted as inhibitors against the leucine-induced activation of p70(S6k). Copyright (C) 1999 Federation of European Biochemical Societies.