Protein kinase inhibitors induce the interphase transition by inactivating mitogen-activated protein kinase in mouse

Q Y Sun1, A Luria, S Rubinstein

  • 1Bar-Ilan University, Ramat-Gan, Israel.

Zygote (Cambridge, England)
|December 17, 1998
PubMed

Insights

Protein kinase inhibitors and a protein tyrosine kinase inhibitor trigger mouse egg activation by inactivating mitogen-activated protein (MAP) kinase. This inactivation is crucial for the metaphase-interphase transition in eggs.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Reproductive Biology

Background:

  • Mouse egg activation is a complex process involving intricate signaling pathways.
  • Mitogen-activated protein (MAP) kinase plays a critical role in regulating cell cycle progression during oocyte maturation and activation.
  • The precise mechanisms by which various kinase inhibitors influence egg activation remain incompletely understood.

Purpose of the Study:

  • To investigate the role of mitogen-activated protein (MAP) kinase in mouse egg activation induced by specific protein kinase inhibitors and a protein tyrosine kinase (PTK) inhibitor.
  • To elucidate the signaling pathways affected by these inhibitors leading to egg activation.

Main Methods:

  • Mouse eggs were treated with varying concentrations of protein kinase inhibitors (Staurosporine, Ro-31-8220) and a PTK inhibitor (genistein).
  • Egg activation, including metaphase-interphase transition and second polar body (PB2) emission, was monitored.
  • MAP kinase activity was assessed using Western blotting with anti-Active MAP kinase and anti-ERK2 antibodies.

Main Results:

  • Higher doses of Staurosporine and Ro-31-8220 induced egg activation, with distinct effects on PB2 emission and cell cycle transition.
  • Genistein also activated approximately half of the treated eggs.
  • A strong correlation was observed between the degree of MAP kinase inactivation and the proportion of eggs entering interphase.

Conclusions:

  • Protein kinase inhibitors and PTK inhibitors induce the interphase transition in mouse eggs primarily by inactivating MAP kinase.
  • Okadaic acid, an artificial activator of MAP kinase, reversed the interphase transition, further supporting the role of MAP kinase inactivation.
  • These findings highlight MAP kinase inactivation as a key event in the artificial activation of mouse eggs by these inhibitors.

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