title: Phosphorylation and inactivation of glycogen synthase kinase-3 by soluble kit ligand in mouse oocytes during early follicular development.
abstract: Communication between mammalian oocytes and their surrounding granulosa cells through the Kit-Kit 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 KL-Kit-PI3 kinase (PI3K)-Akt-Foxo3a 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-3alpha and GSK-3beta, which can result in the inactivation of GSK-3 function in oocytes. In addition, we have shown that the regulation of GSK-3alpha and GSK-3beta in cultured oocytes by soluble KL is accomplished through PI3K, since the PI3K-specific inhibitor LY294002 completely abolished the KL-induced phosphorylation of GSK-3alpha and GSK-3beta. 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 Kit-PI3K-Akt-GSK-3 in oocytes may take part in regulation of oocyte growth and early ovarian follicular development.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
authors.forename: Singareddy
authors.initials: S
authors.lastname: Rajareddy
authors.forename: Pradeep
authors.initials: P
authors.lastname: Reddy
authors.forename: Krishna
authors.initials: K
authors.lastname: Jagarlamudi
authors.forename: Chun
authors.initials: C
authors.lastname: Du
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Guo
authors.forename: Karin
authors.initials: K
authors.lastname: Boman
authors.forename: Eva
authors.initials: E
authors.lastname: Lundin
authors.forename: Ulrika
authors.initials: U
authors.lastname: Ottander
authors.forename: Gunnar
authors.initials: G
authors.lastname: Selstam
authors.forename: Kui
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000201:enzymology*; D006080:Ovarian Follicle / Q000201:enzymology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D019089:Stem Cell Factor / Q000502:physiology*
chemical_list: D019089:Stem Cell Factor; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3