9 S6K Integrates Nutrient and Mitogen Signals to Control Cell Growth

Abstract

For all cells in a specific organ to achieve their mature size and thereby to control the ultimate size of the organism itself, they must coordinate cell growth (increase in cell mass) with the rate of cell proliferation (increase in cell number) (Conlon and Raff 1999; Edgar 1999; Lehner 1999; Polymenis and Schmidt 1999). However, there are examples in biology where these two phenomena have been separated. For example, without cell division, the growing oocyte of Xenopus laevis increases in size 17,000-fold during oogenesis. In contrast, shortly after fertilization, the ensuing embryo passes through 12 synchronous rounds of cell division, dramatically increasing in cell number with no associated growth. Nevertheless, these are exceptions, as growth and proliferation must normally be coordinated within a single cell cycle, such that the new daughter cell will faithfully obtain a full complement of cellular organelles and physiologically important proteins required to carry out its differentiated cellular task (Montagne 2000; Stocker and Hafen 2000; Kozma and Thomas 2002). To achieve these goals, a number of critical growth-promoting anabolic processes must be up-regulated; chief among these is protein synthesis (Thomas 2000).

Rates of protein synthesis must increase not only to generate new cellular organelles and proteins, but also to increase translational capacity (Pardee 1989; Thomas and Hall 1997; Gingras et al. 2001). Indeed, one of the major energy-consuming processes in a growing cell is the generation of nascent ribosomes, with each mature daughter cell containing ~5 million copies of each ribosomal subunit (Schmidt 1999;Warner 1999). This...