IMR Press / FBL / Volume 12 / Issue 13 / DOI: 10.2741/2550

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

The dual-specificity kinases, TOPK and DYRK1A, are critical for oocyte maturation induced by wild-type-but not by oncogenic- ras-p21 protein 

Show Less
1 Research and Development Service and Program in Molecular Cardiology, New York Harbor VA Medical Center, 800 Poly Place, Brooklyn, NY 11209, USA
2 Department of Pathology and Laboratory Medicine (113), New York Harbor VA Medical Center, 800 Poly Place, Brooklyn, NY 11209, USA
3 Department of Pathology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA
4 Department of Microbiology and Human Genetics, Robert Wood Johnson Medical Center, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane – Room 727, Piscataway, NJ 08854 and Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA
5 Departments of Surgery, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203 and VA Medical Center, 800 Poly Place Brooklyn, NY 11209, USA
6 Departments of Pathology, Microbiology and Anatomy and Cell Biology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA
7 Laboratory of Experimental and Computational Biology Building 12B, Room, B103, National Cancer Institute, Bethesda, MD 20892, USA
Academic Editor:Mathew Pincus
Front. Biosci. (Landmark Ed) 2007, 12(13), 5089–5097; https://doi.org/10.2741/2550
Published: 1 September 2007
Abstract

We have previously found that oncogenic ras-p21 and insulin, which activates wild-type ras-21 protein, both induce Xenopus laevis oocyte maturation that is dependent on activation of raf. However, oncogenic ras-p21 utilizes raf-dependent activation of the two classic raf targets, MEK and MAP kinase (MAPK or ERK) while insulin-activated wild-type ras-p21 does not depend on activation of these two kinases. Utilizing a microarray containing the entire Xenopus genome, we discovered two dual specificity kinases, T-Cell Origin Protein Kinase (TOPK), known to bind to raf and the nuclear kinase, DYRK1A, that are expressed at much higher levels in insulin-matured oocytes. Using SiRNA's directed against expression of both of these proteins, we now show that each inhibits insulin-but not oncogenic ras-p21-induced oocyte maturation. Control siRNA's have no effect on either agent in induction of maturation. We find that each SiRNA "knocks down" expression of its target protein while not affecting expression of the other protein. These results suggest that both proteins are required for maturation induced by wild-type, but not oncogenic, ras-p21. They also suggest that oncogenic and wild-type ras-p21 utilize pathways that become divergent downstream of raf. On the basis of these findings, we propose a model for two signal transduction pathways by oncogenic and activated wild-type ras-p21 showing points of overlap and divergence.

Keywords
Oncogenic Ras-P21
Wild-Type Ras-P21
Oocyte Maturation
Dual-Specificity Kinases
TOPK
DYRK1A
Signal Transduction
Share
Back to top