S6 kinase: A regulator of cell growth and cell size

The developmental process of an organism can be considered as two intricate programs, one of which controls the correct patterning of the various organs and the other which regulates the growth of the constitutive tissues. The latter integrates cell growth and proliferation so that mature differentiated cells have an appropriate size. Cell growth depends on the activation of protein synthesis and has been shown to be dominant over cell proliferation, as a cell needs to reach a certain size before it divides. During late G1, cells become committed to complete the cell cycle. In yeast, this restriction point is called START [1]. The number of ribosomes act as a potential sensor for triggering START, as yeast studies have shown that the level of ribosomes is critical for the translation of the START-specific cyclin Cln3 [2]. In mammalian cells, the activation of the 40S ribosomal protein S6 kinase, S6K, has been demonstrated to mediate the translational upregulation of components of the protein synthetic apparatus (See Jaschke and Thomas, this volume), placing the activation of the S6K as a key component in the regulation of cell growth. To analyze the role of the S6K in the whole organism, two similar approaches have provided valuable insights. Firstly, the deletion of the murine S6K1 gene emphasized S6K1's role in growth control, however the discovery of a second compensatory homologous gene product, S6K2, meant that, as yet, the phenotype of a complete murine S6K loss-of-function phenotype has not been determined. Secondly, cloning of the homologous Drosophila S6K gene, has allowed the identification of mutants. These mutants are delayed in development and their body size is significantly reduced due to a reduction in cell size and not in cell number. These results indicate that S6K integrates the control of cell growth with cell size.