scholarly journals Dual Role of Jun N-Terminal Kinase Activity in Bone Morphogenetic Protein-MediatedDrosophilaVentral Head Development

Genetics ◽  
2015 ◽  
Vol 201 (4) ◽  
pp. 1411-1426 ◽  
Author(s):  
Sung Yeon Park ◽  
Brian G. Stultz ◽  
Deborah A. Hursh
Keyword(s):  
Bone Morphogenetic Protein ◽  
Kinase Activity ◽  
Dual Role ◽  
Head Development ◽  
Morphogenetic Protein

scholarly journals The role of bone morphogenetic protein(BMP)cytokine family in folliculogenesis

2017 ◽  
Vol 32 (0) ◽  
pp. 7-12
Author(s):  
Osamu Yoshino ◽  
Ikumi Akiyama ◽  
Yutaka Osuga ◽  
Shigeru Saito
Keyword(s):  
Bone Morphogenetic Protein ◽  
Morphogenetic Protein

scholarly journals Oocyte-Specific Overexpression of Mouse Bone Morphogenetic Protein-15 Leads to Accelerated Folliculogenesis and an Early Onset of Acyclicity in Transgenic Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 2807-2815 ◽  
Author(s):  
Heather E. McMahon ◽  
Osamu Hashimoto ◽  
Pamela L. Mellon ◽  
Shunichi Shimasaki
Keyword(s):  
Transgenic Mice ◽  
Bone Morphogenetic Protein ◽  
Early Onset ◽  
Ovarian Function ◽  
Chimeric Protein ◽  
Mature Protein ◽  
Follicle Growth ◽  
Morphogenetic Protein

Whereas mutations in the bmp15 gene cause infertility in ewes and women due to defects in folliculogenesis, most defects in female mice lacking bone morphogenetic protein (BMP)-15 are confined to the ovulation process, supportive of the observation that functional mouse BMP-15 is barely detected in oocytes in vivo until after the LH surge. In addition, the mouse BMP-15 proprotein is not processed into the functional mature protein in transfected cells. However, a chimeric protein consisting of the human proregion, human cleavage site, and mouse mature region (termed hhmBMP-15) is processed and the mature protein secreted. To study the role of BMP-15 in folliculogenesis, we generated transgenic mice overexpressing hhmBMP-15, exclusively in oocytes during folliculogenesis and confirmed the overexpression of mouse BMP-15 mature protein. Immature transgenic mice exhibited accelerated follicle growth with decreased primary follicles and an increase in secondary follicles. Granulosa cells of immature mice displayed an increased mitotic index and decreased FSH receptor mRNA expression. Adult mice had normal litter sizes but an increased number of atretic antral follicles. Interestingly, aging mice exhibited an early onset of acyclicity marked by increased diestrus length and early occurrence of constant diestrus. These findings indicate the role of BMP-15 in vivo in promoting follicle growth and preventing follicle maturation, resulting in an early decline in the ovarian reserve of transgenic mice. Therefore, the lack of mouse BMP-15 during early folliculogenesis in the wild-type mice may be relevant to their polyovulatory nature as well as the preservation of ovarian function as the mice age.

scholarly journals Cercosporamide inhibits bone morphogenetic protein receptor type I kinase activity in zebrafish

2020 ◽  
Vol 13 (9) ◽  
pp. dmm045971 ◽  
Author(s):  
Jelmer Hoeksma ◽  
Gerard C. M. van der Zon ◽  
Peter ten Dijke ◽  
Jeroen den Hertog
Keyword(s):  
Bone Morphogenetic Protein ◽  
Mammalian Cells ◽  
Kinase Activity ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Type I ◽  
Developmental Defects ◽  
Bone Morphogenetic Protein Receptor ◽  
Protein Receptor ◽  
Morphogenetic Protein ◽  
Constitutively Active

ABSTRACTZebrafish models are well-established tools for investigating the underlying mechanisms of diseases. Here, we identified cercosporamide, a metabolite from the fungus Ascochyta aquiliqiae, as a potent bone morphogenetic protein receptor (BMPR) type I kinase inhibitor through a zebrafish embryo phenotypic screen. The developmental defects in zebrafish, including lack of the ventral fin, induced by cercosporamide were strikingly similar to the phenotypes caused by renowned small-molecule BMPR type I kinase inhibitors and inactivating mutations in zebrafish BMPRs. In mammalian cell-based assays, cercosporamide blocked BMP/SMAD-dependent transcriptional reporter activity and BMP-induced SMAD1/5-phosphorylation. Biochemical assays with a panel of purified recombinant kinases demonstrated that cercosporamide directly inhibited kinase activity of type I BMPRs [also called activin receptor-like kinases (ALKs)]. In mammalian cells, cercosporamide selectively inhibited constitutively active BMPR type I-induced SMAD1/5 phosphorylation. Importantly, cercosporamide rescued the developmental defects caused by constitutively active Alk2 in zebrafish embryos. We believe that cercosporamide could be the first of a new class of molecules with potential to be developed further for clinical use against diseases that are causally linked to overactivation of BMPR signaling, including fibrodysplasia ossificans progressiva and diffuse intrinsic pontine glioma.This article has an associated First Person interview with the first author of the paper.

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