Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K.
It has generally been observed that cells grow to a certain size before they divide. In the last few years, the PI3K signal transduction pathway has emerged as one of the main signaling routes utilized by cells to control their increase in size. Here we focus on two components of this pathway, PKB and S6K, and briefly review the experiments that initially uncovered their roles in cell size control. In addition, we discuss a number of recent observations suggesting that the generic models used to describe this pathway to date may have been oversimplified. Indeed, recent observations in Drosophila and mouse support a more complex interaction between these signaling components in development. Finally, we have utilized two contemporary studies involving PKB- and S6K-deficient mice as a paradigm to underscore the importance of cell size and to accurately delineate the connections between signaling pathways for human disease, such as diabetes mellitus.
Kozma
Sara C
SC
Friedrich Miescher Institute, Basel, Switzerland.
Thomas
George
G
D000818:Animals; D048429:Cell Size; D003920:Diabetes Mellitus / Q000503:physiopathology; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases