scholarly journals The anti-Mullerian hormone type II receptor: insights into the binding domains recognized by a monoclonal antibody and the natural ligand

2004 ◽  
Vol 379 (3) ◽  
pp. 785-793 ◽  
Author(s):  
Imed SALHI ◽  
Sylvie CAMBON-ROQUES ◽  
Isabelle LAMARRE ◽  
Daniel LAUNE ◽  
Franck MOLINA ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Structural Model ◽  
Transforming Growth Factor ◽  
Chinese Hamster ◽  
Transforming Growth Factor Β ◽  
Cross Reactivity ◽  
Ovary Cell ◽  
Type Ii ◽  
Male Embryo ◽  
Binding Interface

Anti-Müllerian hormone (AMH) [also called Müllerian inhibiting substance (MIS)] is a member of the transforming growth factor-β family. AMH and its type II receptor (AMHR-II) are involved in the regression of the Müllerian ducts in the male embryo, and in gonadal functions in the adult. AMH is also known to be a marker of granulosa and Sertoli cell tumours. We selected a high-affinity monoclonal antibody, mAb 12G4, specific for human AMHR-II (hAMHR-II), by FACS analysis, Western blotting and immunohistochemical staining of a hAMHR-II-transfected CHO (Chinese hamster ovary) cell line, normal adult testicular tissue and granulosa cell tumours. Using peptide array screening, we identified the binding sequences of mAb 12G4 and AMH on the receptor. Identification of Asp53 and Ala55 as critical residues in the DRAQVEM minimal epitopic sequence of mAb 12G4 definitively accounted for the lack of cross-reactivity with the murine receptor, in which there is a glycine residue in place of an aspartic acid residue. In a structural model, the AMH-binding interface was mapped to the concave side of hAMHR-II, whereas the mAb 12G4-binding site was located on the convex side. mAb 12G4, the first mAb to be raised against hAMHR-II, therefore has unique properties that could make it a valuable tool for the immunotargeting of tumours expressing this receptor.

Increased type II transforming growth factor-β receptor expression in liver cells during cholesterol challenge

2000 ◽  
Vol 152 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Giovanna Baccante ◽  
Gabriella Mincione ◽  
Concetta Di Febbo ◽  
Anna Coppa ◽  
Domenico Angelucci ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Liver Cells ◽  
Receptor Expression ◽  
Type Ii ◽  
Β Receptor

scholarly journals Abrogation of Transforming Growth Factor-β Type II Receptor Stimulates Embryonic Mouse Lung Branching Morphogenesis in Culture

1996 ◽  
Vol 180 (1) ◽  
pp. 242-257 ◽  
Author(s):  
Jingsong Zhao ◽  
Ding Bu ◽  
Matt Lee ◽  
Harold C. Slavkin ◽  
Frederick L. Hall ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Branching Morphogenesis ◽  
Mouse Lung ◽  
Type Ii ◽  
Embryonic Mouse ◽  
Lung Branching

scholarly journals Downregulation of TRAIL-Receptor 1 Increases TGFβ Type II Receptor Expression and TGFβ Signalling Via MicroRNA-370-3p in Pancreatic Cancer Cells

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 399 ◽  
Author(s):  
David Radke ◽  
Qi Ling ◽  
Robert Häsler ◽  
Gökhan Alp ◽  
Hendrik Ungefroren ◽  
...  
Keyword(s):  
Transient Expression ◽  
Transforming Growth Factor ◽  
Plasminogen Activator Inhibitor ◽  
Transforming Growth Factor Β ◽  
Receptor Expression ◽  
Ductal Adenocarcinoma ◽  
Type Ii ◽  
Plasminogen Activator Inhibitor 1 ◽  
Pancreatic Cancer Cells ◽  
Micro Rnas

The accumulation of perturbations in signalling pathways resulting in an apoptosis-insensitive phenotype is largely responsible for the desperate prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Accumulating evidence suggests that the death receptors TRAIL-R1 and TRAIL-R2 play important roles in PDAC biology by acting as either tumour suppressors through induction of cell death or tumour promoters through induction of pro-inflammatory signalling, invasion and metastasis. TRAIL-R2 can also associate with nuclear proteins and alter the maturation of micro RNAs (miRs). By genome-wide miR profiling and quantitative PCR analyses we now demonstrate that knockdown of TRAIL-R1 in PDAC cells decreased the level of mature miR-370 and led to an increased abundance of the type II receptor for transforming growth factor β (TGFβ). Transfection of cells with an artificial miR-370-3p decreased the levels of TGFβ-RII. We further show that transient expression of the miR-370 mimic decreased TGFβ1-induced expression of SERPINE1 encoding plasminogen activator-inhibitor 1 and partially relieved TGFβ1-induced growth inhibition. Moreover, stable TRAIL-R1 knockdown in Colo357 cells increased TGFβ1-induced SERPINE1 expression and this effect was partially reversed by transient expression of the miR-370 mimic. Finally, after transient knockdown of TRAIL-R1 in Panc1 cells there was a tendency towards enhanced activation of Smad2 and JNK1/2 signalling by exogenous TGFβ1. Taken together, our study reveals that TRAIL-R1 through regulation of miR-370 can decrease the sensitivity of PDAC cells to TGFβ and therefore represents a potential tumour suppressor in late-stage PDAC.

scholarly journals Active immunization against the proregions of GDF9 or BMP15 alters ovulation rate and litter size in mice

Reproduction ◽  
2012 ◽  
Vol 143 (2) ◽  
pp. 195-201 ◽  
Author(s):  
C Joy McIntosh ◽  
Steve Lawrence ◽  
Peter Smith ◽  
Jennifer L Juengel ◽  
Kenneth P McNatty
Keyword(s):  
Litter Size ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cross Reactivity ◽  
Full Length ◽  
Ovulation Rate ◽  
Corpora Lutea ◽  
Immunization Group

The transforming growth factor β (TGFB) superfamily proteins bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), are essential for mammalian fertility. Recent in vitro evidence suggests that the proregions of mouse BMP15 and GDF9 interact with their mature proteins after secretion. In this study, we have actively immunized mice against these proregions to test the potential in vivo roles on fertility. Mice were immunized with either N- or C-terminus proregion peptides of BMP15 or GDF9, or a full-length GDF9 proregion protein, each conjugated to keyhole limpet hemocyanin (KLH). For each immunization group, ovaries were collected from ten mice for histology after immunization, while a further 20 mice were allowed to breed and litter sizes were counted. To link the ovulation and fertility data of these two experimental end points, mice were joined during the time period identified by histology as being the ovulatory period resulting in to the corpora lutea (CL) counted. Antibody titers in sera increased throughout the study period, with no cross-reactivity observed between BMP15 and GDF9 sera and antigens. Compared with KLH controls, mice immunized with the N-terminus BMP15 proregion peptide had ovaries with fewer CL (P<0.05) and produced smaller litters (P<0.05). In contrast, mice immunized with the full-length GDF9 proregion not only had more CL (P<0.01) but also had significantly smaller litter sizes (P<0.01). None of the treatments affected the number of antral follicles per ovary. These findings are consistent with the hypothesis that the proregions of BMP15 and GDF9, after secretion by the oocyte, have physiologically important roles in regulating ovulation rate and litter size in mice.

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