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1 Departments of Medical Biochemistry and Biophysics,
2 Radiation Sciences,
3 Medical Biosciences/Pathology,
4 Clinical Science/Obstetrics and Gynecology,
5 Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden
6 Qilu Hospital, Shandong University, Jinan, 250012 Shandong, China
(Requests for offprints should be addressed to K Liu; Email: kui.liu{at}medchem.umu.se)
(L Liu, S Rajareddy and P Reddy contributed equally to this work)
Communication between mammalian oocytes and their surrounding granulosa cells through the KitKit ligand (KL, or stem cell factor, SCF) system has been shown to be crucial for follicular development. Our previous studies (Reddy et al. 2005, Liu et al. 2006) have indicated that the intra-oocyte KLKitPI3 kinase (PI3K)AktFoxo3a cascade may play an important role in follicular activation and early development. In the present study, using in situ hybridization and in vitro culture of growing oocytes from 8-day-old postnatal mice, we have demonstrated that another Akt substrate, glycogen synthase kinase-3 (GSK-3), is expressed in growing oocytes. Also, treatment of cultured mouse oocytes with soluble KL not only leads to increased Akt kinase activity in the oocytes, which can phosphorylate recombinant GSK-3 in vitro, but also leads to phosphorylation of oocyte GSK-3
and GSK-3ß, which can result in the inactivation of GSK-3 function in oocytes. In addition, we have shown that the regulation of GSK-3
and GSK-3ß in cultured oocytes by soluble KL is accomplished through PI3K, since the PI3K-specific inhibitor LY294002 completely abolished the KL-induced phosphorylation of GSK-3
and GSK-3ß. Moreover, blockage of the Kit signaling pathway by a Kit function-blocking antibody, ACK2, resulted in reduced phosphorylation of GSK-3. Taken together, our data suggest that the cascade from granulosa cell-derived KL to KitPI3KAktGSK-3 in oocytes may take part in regulation of oocyte growth and early ovarian follicular development.
This article has been cited by other articles:
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E. A McLaughlin and S. C McIver Awakening the oocyte: controlling primordial follicle development Reproduction, January 1, 2009; 137(1): 1 - 11. [Abstract] [Full Text] [PDF] |
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