Phosphorylation and activation of human cdc25-C by cdc2-cyclin B and its involvement in the self-amplification of MPF at mitosis

Ingrid Hoffmann, Paul R. Clarke, M. Jesús Marcote, Eric Karsenti, Giulio Draetta

Research output: Contribution to journalArticle

530 Citations (Scopus)

Abstract

We have investigated the mechanisms responsible for the sudden activation of the cdc2-cyclin B protein kinase before mitosis. It has been found previously that cdc25 is the tyrosine phosphatase responsible for dephosphorylating and activating cdc2-cyclin B. In Xenopus eggs and early embryos a cdc25 homologue undergoes periodic phosphorylation and activation. Here we show that the catalytic activity of human cdc25-C phosphatase is also activated directly by phosphorylation in mitotic cells. Phosphorylation of cdc25-C in mitotic HeLa extracts or by cdc2-cyclin B increases its catalytic activity. cdc25-C is not a substrate of the cyclin A-associated kinases. cdc25-C is able to activate cdc2-cyclin B1 in Xenopus egg extracts and to induce Xenopus oocyte maturation, but only after stable thiophosphorylation. This demonstrates that phosphorylation of cdc25-C is required for the activation of cdc2-cyclin B and entry into M-phase. Together, these studies offer a plausible explanation for the rapid activation of cdc2-cyclin B at the onset of mitosis and the self-amplification of MPF observed in vivo.

Original languageEnglish
Pages (from-to)53-63
Number of pages11
JournalEMBO Journal
Volume12
Issue number1
Publication statusPublished - 1 Dec 1993

Fingerprint

Cyclin B
Phosphorylation
Mitosis
Amplification
Chemical activation
Xenopus
Phosphoric Monoester Hydrolases
Catalyst activity
cdc25 Phosphatases
Cyclin B1
Cyclin A
Human Activities
Cell Division
Protein Kinases
Eggs
Oocytes
Ovum
Tyrosine
Phosphotransferases
Embryonic Structures

Keywords

  • Cdc2
  • Cdc25-C
  • Cell cycle
  • Cyclin B
  • Phosphorylation

Cite this

Hoffmann, Ingrid ; Clarke, Paul R. ; Marcote, M. Jesús ; Karsenti, Eric ; Draetta, Giulio. / Phosphorylation and activation of human cdc25-C by cdc2-cyclin B and its involvement in the self-amplification of MPF at mitosis. In: EMBO Journal. 1993 ; Vol. 12, No. 1. pp. 53-63.
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Phosphorylation and activation of human cdc25-C by cdc2-cyclin B and its involvement in the self-amplification of MPF at mitosis. / Hoffmann, Ingrid; Clarke, Paul R.; Marcote, M. Jesús; Karsenti, Eric; Draetta, Giulio.

In: EMBO Journal, Vol. 12, No. 1, 01.12.1993, p. 53-63.

Research output: Contribution to journalArticle

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AU - Clarke, Paul R.

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AB - We have investigated the mechanisms responsible for the sudden activation of the cdc2-cyclin B protein kinase before mitosis. It has been found previously that cdc25 is the tyrosine phosphatase responsible for dephosphorylating and activating cdc2-cyclin B. In Xenopus eggs and early embryos a cdc25 homologue undergoes periodic phosphorylation and activation. Here we show that the catalytic activity of human cdc25-C phosphatase is also activated directly by phosphorylation in mitotic cells. Phosphorylation of cdc25-C in mitotic HeLa extracts or by cdc2-cyclin B increases its catalytic activity. cdc25-C is not a substrate of the cyclin A-associated kinases. cdc25-C is able to activate cdc2-cyclin B1 in Xenopus egg extracts and to induce Xenopus oocyte maturation, but only after stable thiophosphorylation. This demonstrates that phosphorylation of cdc25-C is required for the activation of cdc2-cyclin B and entry into M-phase. Together, these studies offer a plausible explanation for the rapid activation of cdc2-cyclin B at the onset of mitosis and the self-amplification of MPF observed in vivo.

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