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Cell cycle oscillation of phosphatase inhibitor-2 in rat fibroblasts coincident with p34cdc2 restriction

Abstract

ATTENTION has focused on the regulation of the eucaryotic cell division cycle since the protein kinase p34cdc2 was identified as a key enzyme in mitotic induction1–3. The level of this kinase remains constant throughout the cell cycle but its activity alters, particularly before M phase (for a review, see ref. 4). Although the factors regulating cdc2 activity are still unknown, there is increasing evidence that it is influenced by p34cdc2 dephosphorylation5–7. Protein phosphatase inhibitor-2 (12) is a specifie inhibitor of phosphatase type-1 (refs 8, 9), which with type-2A is one of the two principal Ser(P) and Thr(P) phosphatases (reviewed in ref. 10). Here we show that the level of I2, assayed by immuno-fluorescence staining, activity measurements, western immunoblot-ting and metabolic labelling, oscillates during the cell cycle in rat flbroblasts, peaking at S phase and mitosis. Moreover, when we inhibited I2 in vivo by microinjection of anti-I2 antibodies in S-phase cells, the pseudo-mitotic cellular response to injected p34 cdc2 was restored, indicating that I2 might have a role in the modulation of p34 cdc2 activity.

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References

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Brautigan, D., Sunwoo, J., Labbé, JC. et al. Cell cycle oscillation of phosphatase inhibitor-2 in rat fibroblasts coincident with p34cdc2 restriction. Nature 344, 74–78 (1990). https://doi.org/10.1038/344074a0

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