Rho GTPases regulate PRK2/PKN2 to control entry into mitosis and exit from cytokinesis.
Rho GTPases regulate multiple signal transduction pathways that influence many aspects of cell behaviour, including migration, morphology, polarity and cell cycle. Through their ability to control the assembly and organization of the actin and microtubule cytoskeletons, Rho and Cdc42 make several key contributions during the mitotic phase of the cell cycle, including spindle assembly, spindle positioning, cleavage furrow contraction and abscission. We now report that PRK2/PKN2, a Ser/Thr kinase and Rho/Rac effector protein, is an essential regulator of both entry into mitosis and exit from cytokinesis in HeLa S3 cells. PRK2 is required for abscission of the midbody at the end of the cell division cycle and for phosphorylation and activation of Cdc25B, the phosphatase required for activation of mitotic cyclin/Cdk1 complexes at the G2/M transition. This reveals an additional step in the mammalian cell cycle controlled by Rho GTPases.
Schmidt
Anja
A
Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group, University College London, London, UK.
Durgan
Joanne
J
Magalhaes
Ana
A
Hall
Alan
A
D018797:Cell Cycle Proteins / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D020687:cdc25 Phosphatases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; C061570:protein kinase N; D011493:Protein Kinase C; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases; D020741:rho GTP-Binding Proteins