Tr-kit-induced resumption of the cell cycle in mouse eggs requires activation of a Src-like kinase

EMBO J. 2002 Oct 15;21(20):5386-95. doi: 10.1093/emboj/cdf553.


Microinjection in mouse eggs of tr-kit, a truncated form of the c-kit tyrosine kinase present in mouse spermatozoa, causes resumption of meiosis through activation of phospholipase Cgamma1 (PLCgamma1) and Ca(2+) mobilization from intracellular stores. We show that the Src-like kinase Fyn phosphorylates Tyr161 in tr-kit and that this residue is essential for tr-kit function. Fyn is localized in the cortex region underneath the plasma membrane in mouse oocytes. Using several approaches, we demonstrate that Fyn associates with tr-kit and that the interaction requires Tyr161. The interaction between tr-kit and Fyn triggers activation of the kinase as monitored by both autophosphorylation and phosphorylation of PLCgamma1. Co-injection of tr-kit with the SH2 domain of Fyn, or pre-treatment with a Fyn inhibitor, impairs oocyte activation, suggesting that activation of Fyn by tr-kit also occurs in vivo. Finally, microinjection of constitutively active Fyn triggers oocyte activation downstream of tr-kit but still requires PLC activity. We suggest that the mechanism by which tr-kit triggers resumption of meiosis of mouse eggs requires a functional interaction with Fyn and phosphorylation of PLCgamma1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Enzyme Activation / drug effects
  • Female
  • Fertilization / physiology
  • In Vitro Techniques
  • Isoenzymes / metabolism
  • Male
  • Meiosis / drug effects
  • Meiosis / physiology
  • Mice
  • Microinjections
  • Models, Biological
  • Oocytes / cytology*
  • Oocytes / drug effects
  • Oocytes / metabolism*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Phospholipase C gamma
  • Phosphorylation
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-fyn
  • Proto-Oncogene Proteins c-kit / administration & dosage
  • Proto-Oncogene Proteins c-kit / chemistry
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Type C Phospholipases / metabolism
  • Tyrosine / chemistry
  • src-Family Kinases / chemistry
  • src-Family Kinases / metabolism*


  • Isoenzymes
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Tyrosine
  • Proto-Oncogene Proteins c-kit
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn
  • src-Family Kinases
  • Type C Phospholipases
  • Phospholipase C gamma