The Mitogen-Activated p70^s6k / p85^s6k

Abstract

The addition of growth factors to quiescent cells in culture induces their reentry into the cell cycle, followed by DNA synthesis and cell division (Pardee AB, 1989). The approach we have taken in unraveling the mechanisms by which growth factors regulate this response has been to begin with an early obligatory step in cell growth, the activation of protein synthesis (Brooks RF, 1977; Rossow PW et al., 1979), which is not only required for the G_o/G₁ transition, but also for cells to progress through G₁ and enter S (Brooks RF, 1977; Rossow PW et al., 1979). The activation of protein synthesis is controlled at the level of initiation and appears to be triggered by the phosphorylation of a number of key components of the translation machinery including 40S ribosomal protein S6 (Hershey, JWB, 1989; Morley S and Thomas G, 1991). In the case of S6, five moles of phosphate are incorporated into the protein in response to mitogens (Krieg J et al., 1988). The five sites of phosphorylation reside at the carboxy end of the protein and these appear to be phosphorylated in the order Ser₂₃₆ > Ser₂₃₅/Ser₂₄₀ > Ser₂₄₄ > Ser₂₄₇ (Krieg et al. 1988).