CELL CYCLE Cycling with Kinases

Bettencourt-Dias et al. transfected double-stranded RNA for each of the 228 predicted Drosophila kinase genes into cultured S2 cells and found that depletion of 80 of them (in other words, about a third of the Drosophila kinome) led to defects in cell cycle progression or mitosis (or both). The authors used flow cytometry screening to identify cells with delayed progression through specific phases of the cell cycle, as well as blind quantification of 20 parameters (such as centrosomal or spindle defects or mitotic index) to identify abnormalities of mitotic phenotype. In addition to kinases already known to be involved in regulation of the cell cycle or in mitosis and kinases predicted to regulate cytoskeletal elements, the authors identified various cell-signaling kinases involved in cellular responses to growth factors or stress or in responses to nutrients and the regulation of cell growth. These included kinases in the following pathways: nuclear factor-B (NF-B), Janus kinase-signal transducer and activator of transcription (JAK/STAT), p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK), target of rapamycin (TOR)-phosphoinositide-dependent protein kinase 1 (PDK1)-S6K signaling pathways. In addition, the AMP-activated kinase SNF1A was identified. The authors noted that their screen highlights elements of cellular physiology that are closely involved in the regulation of the cell cycle.

M. Bettencourt-Dias, R. Giet, R. Sinka, A. Mazumdar, W. G. Lock, F. Balloux, P. J. Zafiropoulos, S. Yamaguchi, S. Winter, R. W. Carthew, M. Cooper, D. Jones, L. Frenz, D. M. Glover, Genome-wide survey of protein kinases required for cell cycle progression. Nature 432, 980-987 (2004). [PubMed]