Biphasic Activation of the S6 Kinase: Identification of Signalling Pathways

Abstract

In my first lecture I presented data which showed that following mitogenic stimulation of quiescent 3T3 cells, the M_r 70 kd S6 kinase becomes activated by serine/threonine phosphorylation. From this data we deduced two facts: first, that the S6 kinase lies on a kinase cascade initiated by the activation of the tyrosine kinase of the respective growth factor-receptor (Carpenter G and Cohen S, 1990), and second, that there must be at least one other serine/threonine kinase, activated by tyrosine phosphorylation, which couples the S6 kinase with the tyrosine kinase of the receptor, an S6 kinase kinase (Ballou LM et al, 1988a). Such a model would easily fit with earlier kinetic data showing that in quiescent cells stimulated with, for example, EGF, the S6 kinase is rapidly activated, reaching a maximum between five and ten minutes and then slowly decreasing back to basal level by about 60 minutes (Novak-Hofer I and Thomas, G, 1985).