Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: Signalling pathways mediating specific synergistic interactions between GDF9 and BMP15
Author: Mottershead, D.
Ritter, L.
Gilchrist, R.
Citation: Molecular Human Reproduction, 2012; 18(3):121-128
Publisher: Oxford Univ Press
Issue Date: 2012
ISSN: 1360-9947
Statement of
David G. Mottershead, Lesley J. Ritter and Robert B. Gilchrist
Abstract: Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are two proteins selectively expressed in the oocyte which are essential for normal fertility. Both of these proteins are members of the transforming growth factor beta (TGF-β) superfamily and as such are produced as pre-proproteins, existing after proteolytic processing as a complex of the respective pro and mature regions. Previous work has shown that these two proteins interact both at the genetic and cellular signalling levels. In this study, our aim was to determine if the purified mature regions of GDF9 and BMP15 exhibit synergistic interactions on granulosa cells and to determine if such interactions are specific to these two proteins. We have used primary cultures of murine granulosa cells and [3H]-thymidine incorporation or transcriptional reporter assays as our readouts. We observed clear synergistic interactions between the mature regions of GDF9 and BMP15 when either DNA synthesis or SMAD3 signalling were examined. GDF9/BMP15 synergistic interactions were specific such that neither factor could be replaced by an analogous TGF-β superfamily member. The GDF9/BMP15 synergistic signalling response was inhibited by the SMAD2/3 phosphorylation inhibitor SB431542, as well as inhibition of the mitogen-activated protein kinase or rous sarcoma oncogene (SRC) signalling pathways, but not the nuclear factor kappa B pathway. In this study, we show that purified mature regions of GDF9 and BMP15 synergistically interact in a specific manner which is not dependent on the presence of a pro-region. This synergistic interaction is targeted at the SMAD3 pathway, and is dependent on ERK1/2 and SRC kinase signalling.
Keywords: Granulosa Cells
Cells, Cultured
Signal Transduction
Protein Binding
Smad1 Protein
Smad3 Protein
Smad5 Protein
Smad8 Protein
Cumulus Cells
Growth Differentiation Factor 9
Bone Morphogenetic Protein 15
Rights: © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
DOI: 10.1093/molehr/gar056
Appears in Collections:Aurora harvest
Obstetrics and Gynaecology publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.