Paxillin regulates steroid-triggered meiotic resumption in oocytes by enhancing an all-or-none positive feedback kinase loop.
Oocyte 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 and amplify the kinase signaling cascade. To date, little is known regarding other factors that regulate this powerful positive feedback kinase cascade. Here we present the scaffold molecule Paxillin as a newly recognized essential regulator of meiosis in Xenopus laevis oocytes. Reduction of Paxillin expression using RNA interference or antisense oligonucleotides completely abrogates steroid-triggered meiotic resumption. Detailed signaling studies reveal that Paxillin is acting early in the kinase cascade, because 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. These experiments reveal a novel and critical function for Paxillin in meiosis and support the notion that Paxillin may be a general modulator of mitogen-activated protein kinase signaling.
Rasar
Melissa
M
Department of Internal Medicine, Division of Endocrinology and Metabolism, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-8857, USA.
DeFranco
Donald B
DB
Hammes
Stephen R
SR
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D008540:Meiosis; D008957:Models, Genetic; D009865:Oocytes / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism*; D014982:Xenopus laevis
D051419:Paxillin; D013256:Steroids; D012694:Serine