Human pEg3 kinase associates with and phosphorylates CDC25B phosphatase: a potential role for pEg3 in cell cycle regulation.
The pEg3 protein is a member of the evolutionarily conserved KIN1/PAR-1/MARK kinase family which is involved in cell polarity and microtubule dynamics. In Xenopus, pEg3 has been shown to be a cell cycle dependent kinase whose activity increases to a maximum level during mitosis of the first embryonic cell division. CDC25B is one of the three CDC25 phosphatase genes identified in human. It is thought to regulate the G2/M progression by dephosphorylating and activating the CDK/cyclin complexes. In the present study we show that the human pEg3 kinase is able to specifically phosphorylate CDC25B in vitro. One phosphorylation site was identified and corresponded to serine 323. This residue is equivalent to serine 216 in human CDC25C which plays an important role in the regulation of phosphatase during the cell cycle and at the G2 checkpoint. pEg3 is also able to specifically associate with CDC25B in vitro and in vivo. We show that the ectopic expression of active pEg3 in human U2OS cells induces an accumulation of cells in G2. This effect is counteracted by overexpression of CDC25B. Taken together these results suggest that pEg3 is a potential regulator of the G2/M progression and may act antagonistically to the CDC25B phosphatase.
Davezac
Noélie
N
LBCMCP-CNRS UMR5088, IFR109, Université Paul Sabatier, 118 Route de Narbonne, 31062 Toulouse cedex, France.
Baldin
Véronique
V
Blot
Joëlle
J
Ducommun
Bernard
B
Tassan
Jean-Pierre
JP
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003429:Cross Reactions; D006367:HeLa Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D010766:Phosphorylation; D011494:Protein Kinases; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors; D014981:Xenopus / Q000276:immunology; D020687:cdc25 Phosphatases / Q000378:metabolism*
D018797:Cell Cycle Proteins; D051741:Kruppel-Like Transcription Factors; C490820:PEG3 protein, human; D011506:Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D012694:Serine; D011494:Protein Kinases; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases