Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions
Copyright policy )Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions
Significance Although genetic studies have uncovered critical functions of GDF9 and BMP15 in female reproduction, many genetic and physiologic data for these ligands remain perplexing. Here we establish that mouse and human GDF9:BMP15 heterodimers are the most biopotent regulators of ovarian granulosa cell functions. Moreover, GDF9:BMP15 heterodimers require a unique signaling complex that includes the type 2 receptor BMPR2, an ALK4/5/7 type 1 kinase receptor, and an ALK6 type 1 co-receptor. GDF9:BMP15 binding to this complex stimulates phosphorylation of SMAD2/3. Our findings explain intraspecies and interspecies functions of these oocyte-synthesized proteins and have key implications for the regulation of female fertility.
- The University of Texas System United States
- Baylor College of Medicine United States
- Harvard University United States
- University of Cincinnati United States
- Texas A&M University United States
Mice, Knockout, 570, Knockout, Ovary, Life Sciences, Growth Differentiation Factor 9, Smad Proteins, Inbred C57BL, Real-Time Polymerase Chain Reaction, Mice, Inbred C57BL, Mice, HEK293 Cells, Medicine and Health Sciences, Animals, Humans, Female, Bone Morphogenetic Protein 15, Signal Transduction
Mice, Knockout, 570, Knockout, Ovary, Life Sciences, Growth Differentiation Factor 9, Smad Proteins, Inbred C57BL, Real-Time Polymerase Chain Reaction, Mice, Inbred C57BL, Mice, HEK293 Cells, Medicine and Health Sciences, Animals, Humans, Female, Bone Morphogenetic Protein 15, Signal Transduction
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