Paxillin is a Novel Regulator of Xenopus Oocyte Maturation

dc.contributor.advisorHammer, Stephen R.en
dc.creatorYoung, Melissa Rasaren
dc.description.abstractOocyte maturation is triggered by steroids in a transcription-independent fashion that involves an unusual positive feedback loop whereby MOS (a germ cell specific Raf) activates MEK1, which in turn activates ERK2. ERK2 then acts back on MOS to enhance its expression resulting in amplification of the kinase signaling cascade. To date, little is known regarding other factors that regulate this powerful feedback kinase cascade. Here we present the scaffolding molecule, Paxillin, as a newly recognized essential regulator of meiosis in Xenopus leavis oocytes. Reduction of Paxillin expression using RNA interference and antisense oligonucleotides completely abrogates steroid-triggered meiotic resumption. Detailed signaling studies reveal that Paxillin is acting early in the kinase cascade, as it is required for accumulation of MOS protein and complete activation of downstream kinase signaling in response to steroids. Surprisingly, full Paxillin activity also requires serine phosphorylation by a kinase downstream of MOS and MEK1, possibly ERK2. Together, these data suggest that Paxillin is an important regulator of the positive feedback effects of MEK/ERK signaling on MOS protein expression. The ability of Paxillin to function as a MAPK scaffold was analyzed, revealing Paxillin can interact with MOS in mammalian cells. Furthermore, the ability of Paxillin to regulate activity of proteins important for translation, specifically polyadenylation binding proteins, is briefly explored. In all, these experiments reveal a novel and critical function for Paxillin in meiosis, and support the notion that Paxillin may be general modulator of MAPK signaling and/or mRNA translation by polyadenylation binding proteins.en
dc.subject.meshGene Expression Regulationen
dc.titlePaxillin is a Novel Regulator of Xenopus Oocyte Maturationen Regulationen School of Biomedical Sciencesen of Philosophyen