A fluorescence study of type I and type II receptors of bone morphogenetic proteins with bis-ANS (4, 4′-dianilino-1, 1′-bisnaphthyl-5, 5′ disulfonic acid)

2007 ◽  
Vol 1774 (4) ◽  
pp. 493-501 ◽  
Author(s):  
Huiran Yin ◽  
Qing Zhou ◽  
Markandeswar Panda ◽  
Lee-Chuan C. Yeh ◽  
Michelle C. Zavala ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Disulfonic Acid ◽  
Type I ◽  
Type Ii ◽  
Fluorescence Study

scholarly journals Mutant Activin-Like Kinase 2 in Fibrodysplasia Ossificans Progressiva are Activated via T203 by BMP Type II Receptors

2015 ◽  
Vol 29 (1) ◽  
pp. 140-152 ◽  
Author(s):  
Mai Fujimoto ◽  
Satoshi Ohte ◽  
Kenji Osawa ◽  
Arei Miyamoto ◽  
Sho Tsukamoto ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Soft Tissues ◽  
Genetic Disorder ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Type I ◽  
Type Ii ◽  
Activin Receptor ◽  
Bmp Receptors

Abstract Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder characterized by progressive heterotopic ossification in soft tissues, such as the skeletal muscles. FOP has been shown to be caused by gain-of-function mutations in activin receptor-like kinase (ALK)-2, which is a type I receptor for bone morphogenetic proteins (BMPs). In the present study, we examined the molecular mechanisms that underlie the activation of intracellular signaling by mutant ALK2. Mutant ALK2 from FOP patients enhanced the activation of intracellular signaling by type II BMP receptors, such as BMPR-II and activin receptor, type II B, whereas that from heart disease patients did not. This enhancement was dependent on the kinase activity of the type II receptors. Substitution mutations at all nine serine and threonine residues in the ALK2 glycine- and serine-rich domain simultaneously inhibited this enhancement by the type II receptors. Of the nine serine and threonine residues in ALK2, T203 was found to be critical for the enhancement by type II receptors. The T203 residue was conserved in all of the BMP type I receptors, and these residues were essential for intracellular signal transduction in response to ligand stimulation. The phosphorylation levels of the mutant ALK2 related to FOP were higher than those of wild-type ALK2 and were further increased by the presence of type II receptors. The phosphorylation levels of ALK2 were greatly reduced in mutants carrying a mutation at T203, even in the presence of type II receptors. These findings suggest that the mutant ALK2 related to FOP is enhanced by BMP type II receptors via the T203-regulated phosphorylation of ALK2.

scholarly journals Participation of Selected Soluble BMP-2 and BMP-7 Bone Morphogenetic Proteins and Their Soluble Type I ALK-1 and Type II BMPR2 Receptors in Formation and Development of Endometriosis

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1292
Author(s):  
Joanna Janusz ◽  
Aleksandra Janusz ◽  
Zdzisława Kondera-Anasz ◽  
Justyna Sikora ◽  
Marta Smycz-Kubańska ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Peritoneal Fluid ◽  
Reference Group ◽  
Type I ◽  
Type Ii ◽  
Soluble Receptors ◽  
Proliferative Phase ◽  
Pelvic Area ◽  
Angiogenesis Process

Angiogenesis is considered to be one of the key stages in the development of endometriosis. Recent studies indicate that bone morphogenetic proteins (BMPs) and their receptors (BMPR) may play an important role in the angiogenesis process. In the literature, however, there is a lack of publications concerning binding BMPs and their receptors with the pathogenesis of endometriosis. The aim of the study was to determine the role of soluble bone morphogenetic proteins, BMP-2 and BMP-7, and their receptors, ALK-1 and BMPR2, in the process of the formation and development of endometriosis. Peritoneal fluid was collected in the proliferative phase of the menstrual cycle, from 80 women aged 21–49 years (mean age 31.3 ± 6.7 years) undergoing laparoscopy to determine the causes of primary infertility. The study involved 60 women in the I, II, III, and IV stages of the disease. The reference group consisted of 20 women who did not have endometriosis or other lesions in the pelvic area. The concentration in the peritoneal fluid of women with endometriosis was compared to the concentration of this parameter in the reference group, and a statistically significant reduction in the concentration of the BMP-2 molecule was found, as well as increasing concentrations of BMP-7, ALK-1, and BMPR2. BMP-2 and BMP-7 and their soluble receptors, ALK-1 and BMPR2, are involved in the formation of endometriosis. The changes in the concentrations of most of the tested parameters demonstrated in the study, especially in the early stages of the disease, may indicate the more effective formation of new blood vessels in this period.

scholarly journals Expression and localization of activin receptors during endochondral bone development

2001 ◽  
pp. 63-71 ◽  
Author(s):  
M Funaba ◽  
K Ogawa ◽  
M Abe
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Bone Development ◽  
Demineralized Bone Matrix ◽  
Bone Matrix ◽  
Hypertrophic Chondrocytes ◽  
Bone Modeling ◽  
Type I ◽  
Type Ii ◽  
Endochondral Bone ◽  
Activin Receptors

The expression and localization of activins (dimeric protein of inhibin beta subunit) and activin receptors in skeletal tissue were examined. RT-PCR revealed that cultured chondrocytes expressed mRNAs of inhibin/activin betaA and four activin receptors (two type I (ActRI and ActRIB) and two type II (ActRII and ActRIIB)). Immunohistochemical analyses showed that activin betaA, ActRI and ActRII were localized in proliferating chondrocytes and osteoblasts in tibiae of neonatal rats, and in implants of demineralized bone matrix, a well-established model of ectopic bone formation. The immunoreactivities of osteoblasts were decreased with aging in the tibiae and with progressing endochondral bone development in the implants. The strong expression of ActRI was also detected in hypertrophic chondrocytes both in the tibial growth plate and in the implants, whereas immunoreactive ActRII was lower in hypertrophic chondrocytes. Western blot analysis also showed that immunoreactive ActRI, migrating at 52 kDa, was detected only in the implants on days 9 and 11, the period of conversion from cartilage to bone. In view of the sharing of type II receptors between activins and bone morphogenetic proteins (BMPs), our findings suggest that activin/BMP activity involves in bone modeling, especially during active chondro- and osteogenesis and during the conversion from cartilage to bone.

scholarly journals Human BMP8A suppresses luteinization of rat granulosa cells via the SMAD1/5/8 pathway

Reproduction ◽  
2020 ◽  
Vol 159 (3) ◽  
pp. 315-324 ◽  
Author(s):  
Fang-Ju Wu ◽  
Ying-Wen Wang ◽  
Ching-Wei Luo
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Granulosa Cells ◽  
Polycystic Ovarian Syndrome ◽  
Ovarian Function ◽  
Cell Function ◽  
Type I ◽  
Type Ii ◽  
Related Gene ◽  
Inhibitory Effects ◽  
Ovarian Syndrome

Bone morphogenetic proteins (BMPs) are known to play an indispensable role in preventing the precocious luteinization of granulosa cells within growing ovarian follicles. In this study, we found that the transcripts of BMP8 genes are enriched in the ovaries of humans and rodents. When analyzing transcriptomic datasets obtained from human mature granulosa cells, we further found that the BMP8 transcripts not only show the highest abundance among the searchable BMP-related ligands but also decrease significantly in women of advanced age or women with polycystic ovarian syndrome. The correlation between the BMP8 levels in granulosa cells and the decline in ovarian function in these subjects suggests that BMP8 protein may be involved in the regulation of granulosa cell function(s). Using a rat model, we demonstrated that human BMP8A protein activates the SMAD1/5/8 and the SMAD2/3 pathways simultaneously in both immature and mature granulosa cells. Furthermore, the expression of potential type I and type II receptors used by BMP8 in rat granulosa cells was characterized. We found that BMP8A treatment can significantly inhibit gonadotropin-induced progesterone production and steroidogenesis-related gene expression in granulosa cells. Pathway dissection using receptor inhibitors further revealed that such inhibitory effects occur specifically through the BMP8-activated SMAD1/5/8, but not SMAD2/3, pathway. Taken together, considering its abundance and possible functions in granulosa cells, we suggest that BMP8 may act as a novel luteinization inhibitor in growing follicles.

DNA Interaction with 57Co-Bleomycin

1982 ◽  
Vol 21 (06) ◽  
pp. 232-235. ◽  
Author(s):  
J. Kakinuma ◽  
H. Orii
Keyword(s):  
Dna Binding ◽  
Association Constant ◽  
Thermal Denaturation ◽  
Dna Interaction ◽  
Type I ◽  
Type Ii ◽  
Fluorescence Study ◽  
Binding Behavior ◽  
Thermal Denaturation Study ◽  
The Difference

Tumor-diagnostic 57Co-bleomycin is a mixture of two isomers: types I and II. Interaction between these and DNA was studied by fluorescence spectrometry and thermal denaturation. The fluorescence study indicated that cobalt chelation resulted in a remarkable increase in the apparent DNA-bleomycin association constant and a slight increase in bleomy-cin-DNA binding; a remarkable difference was observed between the two isomers. In the thermal denaturation study, the difference of DNA binding behavior was also observed. The tumor affinity of these isomers was slightly different, and type I isomer showed higher tumor affinity than type II. These results indicate that cobalt chelation to bleomycin enhances DNA-bleomycin binding and its DNA binding stability, and these mechanisms, although not fully understood, appear to underly the difference in tumor affinity of cobalt-bleomycin isomers.

scholarly journals High throughput measurements of BMP/BMP receptors interactions using bio-layer interferometry

2020 ◽  
Author(s):  
Valia Khodr ◽  
Paul Machillot ◽  
Elisa Migliorini ◽  
Jean-Baptiste Reiser ◽  
Catherine Picart
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Type I ◽  
Type Ii ◽  
Bone Homeostasis ◽  
Experimental Conditions ◽  
Bmp Receptors ◽  
Physiological Relevance ◽  
Synthetic View ◽  
Similar Affinity

AbstractBone morphogenetic proteins (BMP) are an important family of growth factors playing a role in a large number of physiological and pathological processes, including bone homeostasis, tissue regeneration and cancers. In vivo, BMPs bind successively to both BMP receptors (BMPR) of type I and type II, and a promiscuity has been reported. In this study, we used bio-layer interferometry to perform parallel real-time biosensing and to deduce the kinetic parameters (ka, kd) and the equilibrium constant (KD) for a large range of BMPs/BMPR combinations in similar experimental conditions. We selected four members of the BMP family (BMP-2, 4, 7, 9) known for their physiological relevance and studied their interactions with five type-I BMP receptors (ALK1, 2, 3, 5, 6) and three type-II BMP receptors (BMPR-II, ACTR-IIA, ACTR-IIB). We reveal that BMP-2 and BMP-4 behave differently, especially regarding their kinetic interactions and affinities with the type-II BMPR. We found that BMP-7 has a higher affinity for ACTR-IIA and a tenfold lower affinity with the type-I receptors. While BMP-9 has a high and similar affinity for all type-II receptors, it can interact with ALK5 and ALK2, in addition to ALK1. Interestingly, we also found that all BMPs can interact with ALK5. The interaction between BMPs and both type-I and type II receptors immobilized on the same surface did not reveal further cooperativity. Our work provides a synthetic view of the interactions of these BMPs with their receptors and paves the way for future studies on their cell-type and receptor specific signaling pathways.

BMP Receptors in Limb and Tooth Formation

1999 ◽  
Vol 10 (2) ◽  
pp. 182-198 ◽  
Author(s):  
S. Cheifetz
Keyword(s):  
Signal Transduction ◽  
Ligand Binding ◽  
Bone Morphogenetic Proteins ◽  
Type I ◽  
Type Ii ◽  
Tooth Formation ◽  
Receptor Complexes ◽  
Bmp Receptors ◽  
Receptor Kinases ◽  
Multiple Type

Members of the TGF-β superfamily signal through receptor complexes comprised of type I and type II receptors. These receptors, which are serine/threonine kinases, form two new classes of transmembrane receptor kinases. The activity of both of the kinases is necessary for signal transduction in response to ligand binding. Bone morphogenetic proteins (BMPs), which are members of the TGF-β superfamily, bind to multiple type I and type II receptors. There is growing evidence to support the hypothesis that the BMP receptors are differentially regulated during development and that they have both unique and overlapping functions. Thus, the nature and distribution of the BMP receptors, which are reviewed here in the context of the development of limbs and teeth, appear to be critical in the control of the diverse activities of BMPs.

Parapodial swim muscle in Aplysia brasiliana. II. Ca(2+)-dependent K+ currents in isolated muscle fibers and their blockade by chloride substitutes

1996 ◽  
Vol 76 (3) ◽  
pp. 1531-1539 ◽  
Author(s):  
P. J. Laurienti ◽  
J. E. Blankenship
Keyword(s):  
Muscle Fibers ◽  
Outward Current ◽  
Disulfonic Acid ◽  
Delayed Rectifier ◽  
Unexpected Finding ◽  
Type I ◽  
Type Ii ◽  
Type I Fibers ◽  
Type Ii Fibers ◽  
K Currents

1. We describe here the properties of two Ca(2+)-dependent K+ currents found in type II muscle fibers dissociated from the parapodia (swim appendages) of the marine snail Aplysia brasiliana. 2. Type II parapodial muscle fibers display three voltage-dependent currents that are also seen in type I fibers, a delayed rectifier current [IK(V)], a transient A current (IA), and a prominent L-type Ca2+ current. In addition, type II fibers also have two outward K+ currents, a transient, inactivating one and a slower, noninactivating one [IK(Ca,t) and IK(Ca,s), respectively], that are Ca2+ dependent. The expression of these currents in normal type II fibers generally produces a waveform of total outward current that is faster to peak than the total outward current seen in response to voltage steps in type I fibers and that does not inactivate at the end of an 80-ms voltage step. 3. Both IK(Ca,t) and IK(Ca,s) are absent when external Ca2+ is eliminated or when extracellular Ca2+ concentration ([Ca2+]o) is substituted with 10 mM Co2+ or Ba2+. Their threshold for activation is around -40 mV. IK(Ca,t) peaks rapidly and then inactivates, but IK(Ca,s) rises slowly and does not inactivate for as long as 200 ms. Both currents, like IK(V) and IA, are sensitive to tetraethylammonium and 4-aminopyridine and are not readily separated from either the voltage-gated currents or from one another by these pharmacological agents. 4. Tail current analysis from depolarized voltage steps in varying (K+]o demonstrates that these currents are carried by K+ ions and not by Cl-. 5. An unexpected finding, however, is that these Ca(2+)-dependent K+ currents are blocked by standard Cl- ion substitutes, such as methanesulfonate, isethionate, and propionate. IK(Ca,s) is slightly more sensitive to these Cl- substitutes than is IK(Ca,t). The chloride blocker 4,4'-diisothiocyantastilbene-2,2'disulfonic acid also partially blocked the Ca(2+)-dependent K+ currents. 6. The presence of these Ca(2+)-dependent K+ currents in type II fibers may contribute to a more rapid repolarization following depolarization-induced contractions. In contrast to type I fibers, which have smaller calcium current and no Ca(2+)-activated K+ currents, type II muscle cells may function more like "fast" fibers and relax more rapidly.

Heat-Etching with a Bullivant Type II Simple Freeze-Cleave Device

1970 ◽  
Vol 28 ◽  
pp. 106-107 ◽  
Author(s):  
Ronald S. Weinstein ◽  
N. Scott McNutt
Keyword(s):  
New Zealand ◽  
General Hospital ◽  
Massachusetts General Hospital ◽  
Type I ◽  
Type Ii ◽  
Collaborative Effort ◽  
Temperature And Pressure ◽  
The University

The Type I simple cold block device was described by Bullivant and Ames in 1966 and represented the product of the first successful effort to simplify the equipment required to do sophisticated freeze-cleave techniques. Bullivant, Weinstein and Someda described the Type II device which is a modification of the Type I device and was developed as a collaborative effort at the Massachusetts General Hospital and the University of Auckland, New Zealand. The modifications reduced specimen contamination and provided controlled specimen warming for heat-etching of fracture faces. We have now tested the Mass. General Hospital version of the Type II device (called the “Type II-MGH device”) on a wide variety of biological specimens and have established temperature and pressure curves for routine heat-etching with the device.

Labelling of non-A, non-B hepatitis infected chimpanzee hepatocytes with nuclease-gold conjugates

1984 ◽  
Vol 42 ◽  
pp. 250-251
Author(s):  
G. D. Gagne ◽  
M. F. Miller ◽  
D. A. Peterson
Keyword(s):  
Endoplasmic Reticulum ◽  
Experimental Infection ◽  
Uranyl Acetate ◽  
Type I ◽  
Cellular Injury ◽  
Type Ii ◽  
Tubular Structures ◽  
Type Iii ◽  
Type Iv ◽  
Infected Chimpanzee

Experimental infection of chimpanzees with non-A, non-B hepatitis (NANB) or with delta agent hepatitis results in the appearance of characteristic cytoplasmic alterations in the hepatocytes. These alterations include spongelike inclusions (Type I), attached convoluted membranes (Type II), tubular structures (Type III), and microtubular aggregates (Type IV) (Fig. 1). Type I, II and III structures are, by association, believed to be derived from endoplasmic reticulum and may be morphogenetically related. Type IV structures are generally observed free in the cytoplasm but sometimes in the vicinity of type III structures. It is not known whether these structures are somehow involved in the replication and/or assembly of the putative NANB virus or whether they are simply nonspecific responses to cellular injury. When treated with uranyl acetate, type I, II and III structures stain intensely as if they might contain nucleic acids. If these structures do correspond to intermediates in the replication of a virus, one might expect them to contain DNA or RNA and the present study was undertaken to explore this possibility.

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